Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used si...Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.展开更多
Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and ...Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and heme molecules to assemble hemoglobin(Zhang et al., 2021). The erythroid-specific enzyme δ-aminolevulinate synthase 2 (ALAS2) is a key rate-limiting factor in heme biosynthesis,with its expression increasing in late-stage erythropoiesis to meet heme demands (Sadlon et al., 1999). Zebrafish (Danio rerio) is a well-established model for studying erythropoiesis due to its genetic tractability and optical transparency (Zhang and Hamza, 2019;Zhang et al., 2021). The Tol2-mediated Gal4-UAS system has been widely applied for gene and enhancer trapping in zebrafish (Asakawa and Kawakami, 2009). However, reliable Gal4 enhancer-trap lines for erythropoiesis remain limited. Here, we report a transgenic zebrafish line with erythroid-specific Gal4FF expression under the control of the endogenous alas2 promoter, offering a more precise erythroblast labeling than the gata1a reporter line. This model provides a valuable tool for erythroid-specific investigations of blood flow dynamics and gene function.展开更多
A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c ...A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c mice in a single dose resulted in a dose-dependent increase in the number of circulating reticulocytes.Within the erythropoiesis stimulating protein dose range of 3.125 to 200 ng per mouse,there is a strong linear relationship between the dose and reticulocyte counts in the treated mice.This linear relationship allows us to determine the biological potency of the testing erythropoiesis stimulating protein preparation relative to a reference standard using parallel line assay.Accuracy,precision,dose variation and blood collection time of this method were analyzed in order to choose doses in the linear range that are suitable for setting up a useful,precise,and economical bioassay.展开更多
Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- asso...Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.展开更多
Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse...Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse erythroleukemia cells and have lost the capacity to respond to erythropoietin.Moreover,the research in the field of erythropoiesis has been severely hampered by the paucity of erythroblasts obtained from chick embryos,human,mouse,rat fetal liver,mouse spleen,or the bone marrow.In our paper,the fetal blood from newly slaughtered pregnant sheep meets the needs of studies as abundant staring biological materials at the nucleotide level and also reflects in vivo proliferative and differential status of erythroblasts.Appling the technique of mRNA differential display with minor modification,we directly compared cDNA fragmerts from the fetal blood erythroblasts and adult pregnant sheep leukocytes by PCR on DNA sequencing gels and revealed two differentially expressing bands.One is a novel gene fragment, which has homology with UV-sensitive cone opsin or rhodopsin by examinating the predicted amino acid sequence.Since the blood cells are sensitive to radiation,it can be safely inferred that this fragment participate in the process of cytocidal effect of the radiation.The other fragment is glucose induced gene /elongation factor 2 3′end noncoding region,which was first cloned from glucose induced bovine aortic smooth muscle cells.Using Northern blot hybridization method,authentic specific expression was confirmed.展开更多
Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cy...Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin- CDK complex, arresting cell cycle. Terminal erythropoiesis is closely coordinated with cell cycle exit, which is regulated by cyclins, CDKs, and CDKIs [1]. In the global transcriptome of human terminal erythropoiesis [2], p19INK4d is expressed highly, and its expression is significantly up-regulated during human terminal erythropoiesis. However, the roles of p19INK4d in terminal erythropoiesis are still unknown.展开更多
Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological condition...Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.展开更多
The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobi...The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobin and soluble transferrin receptor were normal, whereas serum iron and total iron binding capacity (TIBC) were subnormal, and mean ferritin was above the upper reference limit. Iron-restricted erythropoiesis (IRE), defined as a bone marrow smear staining positive for iron in combination with transferrin saturation less than 20%, was present in all patients. All patients exhibited clinical and biochemical signs of active inflammation with elevated C-reactive protein and an increased erythrocyte sedimentation rate.展开更多
Erythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to adult stages.Investi...Erythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to adult stages.Investigations into its molecular mechanisms have generated a wealth of expression data,including bulk and single-cell RNA sequencing data.A comprehensively integrated and well-curated erythropoiesis-specific database will greatly facilitate the mining of gene expression data and enable large-scale research of erythropoiesis and erythroid-related diseases.Here,we present EryDB,an open-access and comprehensive database dedicated to the collection,integration,analysis,and visualization of transcriptomic data for erythropoiesis and erythroid-related diseases.Currently,the database includes expertly curated quality-assured data of 3803 samples and 1,187,119 single cells derived from 107 public studies of three species(Homo sapiens,Mus musculus,and Danio rerio),nine tissue types,and five diseases.EryDB provides users with the ability to not only browse the molecular features of erythropoiesis between tissues and species,but also perform computational analyses of single-cell and bulk RNA sequencing data,thus serving as a convenient platform for customized queries and analyses.EryDB v1.0 is freely accessible at https://ngdc.cncb.ac.cn/EryDB/home.展开更多
Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism k...Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism known as stress erythropoiesis.This crucial physiological process results in increased erythrocyte production,particularly in extramedullary sites such as the spleen and liver,to restore adequate oxygen levels.Unlike steady-state erythropoiesis,which primarily occurs in the bone marrow,stress erythropoiesis depends on distinct progenitor cells and signaling pathways within a specialized erythroid niche in adult spleen and liver.This niche provides essential support for the proliferation,differentiation,and maturation of erythroid progenitors during anemic stress.The dynamics within this niche under stress conditions involve complex interactions between progenitor and niche cells.These interactions are regulated by specific molecular signals that adapt to the body’s physiological demands,ensuring an appropriate response to stress.This review explores the cellular and molecular mechanisms governing these processes,highlighting the extrinsic pathways and cellular interactions during stress erythropoiesis.In addition,it underscores the need for future research to translate findings from murine models into therapeutic strategies for treating anemia-related diseases.展开更多
Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the ...Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.展开更多
Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of eryth...Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.展开更多
EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto active...EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.展开更多
Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is preci...Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.展开更多
The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding RNAs.Among them,long noncoding RNAs(lncRNAs)consist of a significant portion that widely exists across mammal genome,g...The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding RNAs.Among them,long noncoding RNAs(lncRNAs)consist of a significant portion that widely exists across mammal genome,generating from high-throughput transcriptomic studies in the last decade.Although the functions of most lncRNAs remain to be further investigated,many of them have already been shown to play critical roles during normal development and disease conditions.Increasing evidence indicates that lncRNAs involve in versatile biological processes during erythroid proliferation and differentiation,including erythroid cell survival,heme metabolism,globin switching and regulation,erythroid enucleation,etc,via cis-or trans-mediated molecular mechanisms.In this review,we focus on recent advances regarding the functions and mechanisms of lncRNAs in normal erythropoiesis.展开更多
BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lin...BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages. OBJECTIVE： This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis. METHODS： Relevant English-language studies were identified and retrieved from the PubMed search engine （1981-2017） using the following keywords： ＂Erythropoiesis＂, ＂Catecholamines＂, ＂Nervous system＂, and ＂Cytokines.＂ RESULTS： Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis. CONCLUSION： Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells （RBCs） in both chronic and physiological catecholamine activation.展开更多
The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequen...The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucleation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized erythroid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.展开更多
MicroRNAs （miRNAs） are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiat...MicroRNAs （miRNAs） are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiation process of erythroid progenitors to nucleate red blood cells. Maturation, proliferation and differentiation of red blood cells is affected by erythroid factors, signaling pathways in niche of hematopoietic cells, transcription factors as well as miRNAs. Expression of different types of miRNAs during erythroid development provides a background for the study of these molecules to control erythroid differentiation and maturation as well as their use as diagnostic and prognostic markers to treat erythroid disorders like thalassemia, sickle cell disease and erythrocyte enzyme deficiencies. In this paper, with reference to biosynthesis of miRNAs, their function in normal and anemic erythropoiesis has been investigated. The target molecule of each of these miRNAs has been cited in an attempt to elucidate their role in erythropoiesis.展开更多
Anemia,usually due to iron deficiency,is highly prevalent among patients with colorectal cancer.Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron uti...Anemia,usually due to iron deficiency,is highly prevalent among patients with colorectal cancer.Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization.Preoperative anemia predicts for decreased survival.Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes,increased post-operative nosocomial infections,longer hospital stays,increased rates of cancer recurrence and perioperative venous thromboembolism.Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management,minimizes or eliminates allogeneic blood transfusion.This includes restrictive transfusion policy,thromboprophylaxis and anemia management to improve outcomes.Normalization of preoperative hemoglobin levels is a World Health Organization recommendation.Iron repletion should be routinely ordered when indicated.Oral iron is poorly tolerated with low adherence based on published evidence.Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions.Serious adverse events with intravenous iron are extremely rare.Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care.Erythropoiesis stimulating agents may improve response rates.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.展开更多
By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledg...By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.展开更多
基金supported by the Institute for Basic Science (IBS-R022-D1)Global Learning&Academic Research Institution for Master’s/Ph D students and Post-Doc Program of the National Research Foundation of Korea Grant funded by the Ministry of Education (RS-2023-00301938)+1 种基金National Research Foundation of Korea Grant funded by the Korean government (RS-2024-00406152,MSIT)Additional financial support was provided by the 2024 Post-Doc Development Program of Pusan National University,Korea Medical Institute,and KREONET。
文摘Polystyrene nanoparticles pose significant toxicological risks to aquatic ecosystems,yet their impact on zebrafish(Danio rerio)embryonic development,particularly erythropoiesis,remains underexplored.This study used single-cell RNA sequencing to comprehensively evaluate the effects of polystyrene nanoparticle exposure on erythropoiesis in zebrafish embryos.In vivo validation experiments corroborated the transcriptomic findings,revealing that polystyrene nanoparticle exposure disrupted erythrocyte differentiation,as evidenced by the decrease in mature erythrocytes and concomitant increase in immature erythrocytes.Additionally,impaired heme synthesis further contributed to the diminished erythrocyte population.These findings underscore the toxic effects of polystyrene nanoparticles on hematopoietic processes,highlighting their potential to compromise organismal health in aquatic environments.
基金supported by the National Key Research and Development Plan of China (2023YFA1802000)the National Natural Science Foundation of China for Distinguished Young Scholars (31925014),the National Natural Science Foundation of China Key Program (32130033),the National Natural Science Foundation of Original Exploratory Program (32350006)+5 种基金the Key Research Program of Frontier Sciences,Chinese Academy of Sciences (ZDBS-LY-SM010)Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences,Shanghai Branch (JCYJ-SHFY-2022-006)Shanghai Science Technology Innovation Action Plan for Basic Research Program (21JC1406300)Haihe laboratory of Cell Ecosystem Innovation Fund (24HHXBSS00011)CAS project for Young Scientists in Basic Research (YSBR-077)supported by Science and Technology Commission of Shanghai Municipality (Shanghai Rising-Star Program,23QA1411300)
文摘Erythroid cells, the predominant circulating blood cells, are essential for oxygen and carbon dioxide transport (Obeagu, 2024).Their production, erythropoiesis, involves the coordinated synthesis of globin chains and heme molecules to assemble hemoglobin(Zhang et al., 2021). The erythroid-specific enzyme δ-aminolevulinate synthase 2 (ALAS2) is a key rate-limiting factor in heme biosynthesis,with its expression increasing in late-stage erythropoiesis to meet heme demands (Sadlon et al., 1999). Zebrafish (Danio rerio) is a well-established model for studying erythropoiesis due to its genetic tractability and optical transparency (Zhang and Hamza, 2019;Zhang et al., 2021). The Tol2-mediated Gal4-UAS system has been widely applied for gene and enhancer trapping in zebrafish (Asakawa and Kawakami, 2009). However, reliable Gal4 enhancer-trap lines for erythropoiesis remain limited. Here, we report a transgenic zebrafish line with erythroid-specific Gal4FF expression under the control of the endogenous alas2 promoter, offering a more precise erythroblast labeling than the gata1a reporter line. This model provides a valuable tool for erythroid-specific investigations of blood flow dynamics and gene function.
文摘A simple in vivo bioassay suitable for the routine quality control testing of a new erythropoiesis stimulating protein was developed.Subcutaneous administration of the new erythropoiesis stimulating protein to Balb/c mice in a single dose resulted in a dose-dependent increase in the number of circulating reticulocytes.Within the erythropoiesis stimulating protein dose range of 3.125 to 200 ng per mouse,there is a strong linear relationship between the dose and reticulocyte counts in the treated mice.This linear relationship allows us to determine the biological potency of the testing erythropoiesis stimulating protein preparation relative to a reference standard using parallel line assay.Accuracy,precision,dose variation and blood collection time of this method were analyzed in order to choose doses in the linear range that are suitable for setting up a useful,precise,and economical bioassay.
文摘Anemia is a frequent complication in patients with inflammatory bowel disease (IBD), and is associated with decreased quality of life and increased rate of hospitalization. The primary therapeutic targets of IBD- associated anemia are iron deficiency and anemia of chronic disease. An important prognostic parameter of the success or failure of therapy is the outcome of the underlying disease. Iron deficiency should be appropriately managed with iron supplementation. However, the use of oral iron therapy is limited by several problems, the most important being gastrointestinal side effects leading occasionally to disease relapse and poor iron absorption. Intravenous iron preparations are more reliable, with iron sucrose demonstrating the best efficacy and tolerability. Treatment with erythropoietin or darbepoetin has been proven to be effective in patients with anemia, who fail to respond to intravenous iron. Patients with ongoing inflammation have anemia of chronic disease and may require combination therapy comprising of intravenous iron sucrose and erythropoietin. After initiating treatment, careful monitoring of hemoglobin levels and iron parameters is needed in order to avoid recurrence of anemia. In conclusion, anemia in the setting of IBD should be aggressively diagnosed, investigated, and treated. Future studies should define the optimal dose and schedule of intravenous iron supplementation and appropriate erythropoietin therapy in these patients.
文摘Most studies of erythropoiesis have been performed either with the virally transformed MEL cells or with the scarce erythroblasts within unhomogeneous cell populations.MEL cells are the Friend virus transformed mouse erythroleukemia cells and have lost the capacity to respond to erythropoietin.Moreover,the research in the field of erythropoiesis has been severely hampered by the paucity of erythroblasts obtained from chick embryos,human,mouse,rat fetal liver,mouse spleen,or the bone marrow.In our paper,the fetal blood from newly slaughtered pregnant sheep meets the needs of studies as abundant staring biological materials at the nucleotide level and also reflects in vivo proliferative and differential status of erythroblasts.Appling the technique of mRNA differential display with minor modification,we directly compared cDNA fragmerts from the fetal blood erythroblasts and adult pregnant sheep leukocytes by PCR on DNA sequencing gels and revealed two differentially expressing bands.One is a novel gene fragment, which has homology with UV-sensitive cone opsin or rhodopsin by examinating the predicted amino acid sequence.Since the blood cells are sensitive to radiation,it can be safely inferred that this fragment participate in the process of cytocidal effect of the radiation.The other fragment is glucose induced gene /elongation factor 2 3′end noncoding region,which was first cloned from glucose induced bovine aortic smooth muscle cells.Using Northern blot hybridization method,authentic specific expression was confirmed.
基金supported in part by the National Natural Science Foundation of China(Grant Nos.81270576 and 81470362)
文摘Normally, cyclin interacts with cyclin-dependent kinase (CDK) to form a cyclin-CDK complex, which promotes cell cycle progression, whereas cyclin-dependent kinase inhibitor (CDKI) molecules inhibit the formation of cyclin- CDK complex, arresting cell cycle. Terminal erythropoiesis is closely coordinated with cell cycle exit, which is regulated by cyclins, CDKs, and CDKIs [1]. In the global transcriptome of human terminal erythropoiesis [2], p19INK4d is expressed highly, and its expression is significantly up-regulated during human terminal erythropoiesis. However, the roles of p19INK4d in terminal erythropoiesis are still unknown.
文摘Coexistence of chronic kidney disease (CKD) and chronic heart failure (CHF) define a recently recognized clinical entity known as cardio-renal syndrome. Sufficient evidence suggests that the two pathological conditions share common pathogenic etiology which is not yet fully defined. Superimposed anaemia is a common finding among patients suffering from cardio-renal syndrome. The combination of CKD, CHF and anaemia increase the probability of death by 6 times compared to normal individuals. Early attempts to restore anaemia either by iron supplementation, erythropoiesis stimulating agents (ESAs) or combination of the two have reported to improve quality of life, morbidity and mortality especially among patients treated by cardiologists. Recent publications of well controlled epidemiological studies failed to prove convincing beneficial effect of the above mentioned therapy moreover skepticism has raised concerning the safety of restoring anaemia among patients with cardio-renal syndrome as well as used medications. There are still unresolved problems concerning the definition of anaemia, by means of hemoglobin level among these patients, the target hemoglobin level and the therapeutic regimen of ESAs administration and iron supplementation. We need much more evidence in order to define an effective and safe treatment strategy correcting anaemia among patients with cardio-renal syndrome.
文摘The aim of this observational study was to biochemically characterize the anaemia in GCA (giant cell arteritis) and PMR (polymyalgia rheumatica) patients. Values for mean corpuscular volume, mean corpuscular hemoglobin and soluble transferrin receptor were normal, whereas serum iron and total iron binding capacity (TIBC) were subnormal, and mean ferritin was above the upper reference limit. Iron-restricted erythropoiesis (IRE), defined as a bone marrow smear staining positive for iron in combination with transferrin saturation less than 20%, was present in all patients. All patients exhibited clinical and biochemical signs of active inflammation with elevated C-reactive protein and an increased erythrocyte sedimentation rate.
基金supported by the National Key R&D Program of China(Grant No.2022YFC2406803)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16010602)the National Natural Science Foundation of China(Grant Nos.81870097,82070114,and 82270126).
文摘Erythropoiesis is a finely regulated and complex process that involves multiple transformations from hematopoietic stem cells to mature red blood cells at hematopoietic sites from the embryonic to adult stages.Investigations into its molecular mechanisms have generated a wealth of expression data,including bulk and single-cell RNA sequencing data.A comprehensively integrated and well-curated erythropoiesis-specific database will greatly facilitate the mining of gene expression data and enable large-scale research of erythropoiesis and erythroid-related diseases.Here,we present EryDB,an open-access and comprehensive database dedicated to the collection,integration,analysis,and visualization of transcriptomic data for erythropoiesis and erythroid-related diseases.Currently,the database includes expertly curated quality-assured data of 3803 samples and 1,187,119 single cells derived from 107 public studies of three species(Homo sapiens,Mus musculus,and Danio rerio),nine tissue types,and five diseases.EryDB provides users with the ability to not only browse the molecular features of erythropoiesis between tissues and species,but also perform computational analyses of single-cell and bulk RNA sequencing data,thus serving as a convenient platform for customized queries and analyses.EryDB v1.0 is freely accessible at https://ngdc.cncb.ac.cn/EryDB/home.
文摘Anemia is a condition marked by a shortage of red blood cells or hemoglobin,resulting in a diminished ability of the blood to carry oxygen.In response to anemia or hypoxia,the body activates a compensatory mechanism known as stress erythropoiesis.This crucial physiological process results in increased erythrocyte production,particularly in extramedullary sites such as the spleen and liver,to restore adequate oxygen levels.Unlike steady-state erythropoiesis,which primarily occurs in the bone marrow,stress erythropoiesis depends on distinct progenitor cells and signaling pathways within a specialized erythroid niche in adult spleen and liver.This niche provides essential support for the proliferation,differentiation,and maturation of erythroid progenitors during anemic stress.The dynamics within this niche under stress conditions involve complex interactions between progenitor and niche cells.These interactions are regulated by specific molecular signals that adapt to the body’s physiological demands,ensuring an appropriate response to stress.This review explores the cellular and molecular mechanisms governing these processes,highlighting the extrinsic pathways and cellular interactions during stress erythropoiesis.In addition,it underscores the need for future research to translate findings from murine models into therapeutic strategies for treating anemia-related diseases.
文摘Beta thalassemia(β-thalassemia)syndromes are a heterogeneous group of inherited hemoglobinopathies caused by molecular defects in the beta-globin gene that lead to the impaired synthesis of beta-globin chains of the hemoglobin.The hallmarks of the disease include ineffective erythropoiesis,chronic hemolytic anemia,and iron overload.Clinical presentation ranges from asymptomatic carriers to severe anemia requiring lifelong blood transfusions with subsequent devastating complications.The management of patients with severeβ-thalassemia represents a global health problem,particularly in low-income countries.Until recently,management strategies were limited to regular transfusions and iron chelation therapy,with allogeneic hematopoietic stem cell transplantation available only for a subset of patients.Better understanding of the underlying pathophysiological mechanisms ofβ-thalassemia syndromes and associated clinical phenotypes has paved the way for novel therapeutic options,including pharmacologic enhancers of effective erythropoiesis and gene therapy.
基金supported by grants from the National Natural Science Foundation of China(814703628117190581272187)
文摘Erythropoiesis is a process during which multipotential hematopoietic stem cells proliferate, differentiate and eventually form mature erythrocytes. Interestingly, unlike most cell types, an important feature of erythropoiesis is that following each mitosis the daughter cells are morphologically and functionally different from the parent cell from which they are derived, demonstrating the need to study erythropoiesis in a stage-specific manner. This has been impossible until recently due to lack of methods for isolating erythroid cells at each distinct developmental stage. This review summarizes recent advances in the development of methods for isolating both murine and human erythroid cells and their applications. These methods provide powerful means for studying normal and impaired erythropoiesis associated with hematological disorders.
基金supported by the Nation Natural Science Foundation of China(Program No.32070807)by the National Key R&D Program of China(2018YFD0900101)by the project 2020SKLBC-KF06 of State Key Laboratory of Biocontrol.
文摘EAF1 and EAF2,the eleven-nineteen lysine-rich leukemia(ELL)-associated factors which can assemble to the super elongation complex(AFF1/4,AF9/ENL,ELL,and P-TEFb),are reported to participate in RNA polymeraseⅡto actively regulate a variety of biological processes,including leukemia and embryogenesis,but whether and how EAF1/2 function in hematopoietic system related hypoxia tolerance during embryogenesis remains unclear.Here,we unveiled that deletion of EAF1/2(eaf1^(-/-)and eaf2^(-/-))caused reduction in hypoxia tolerance in zebrafish,leading to reduced erythropoiesis during hematopoietic processes.Meanwhile,eaf1^(-/-)and eaf2^(-/-)mutants showed significant reduc-tion in the expression of key transcriptional regulators scl,lmo2,and gata1a in erythropoiesis at both 24 h post fertilization(hpf)and 72 hpf,with gata1a downregulated while scl and lmo2 upregulated at 14 hpf.Mechanistically,eaf1^(-/-)and eaf2^(-/-)mutants exhibited significant changes in the expression of epigenetic modified histones,with a significant increase in the binding enrichment of modified histone H3K27me3 in gata1a promoter rather than scl and lmo2 promoters.Additionally,eaf1^(-/-)and eaf2^(-/-)mutants exhibited a dynamic expression of canonical WNT/β-catenin signaling during erythropoiesis,with significant reduction in p-β-Catenin level and in the binding enrichment of both scl and lmo2 promoters with the WNT transcriptional factor TCF4 at 24 hpf.These findings demonstrate an important role of Eaf1/2 in erythropoiesis in zebrafish and may have shed some light on regeneration medicine for anemia and related diseases and on molecular basis for fish economic or productive traits,such as growth,disease resistance,hypoxia tolerance,and so on.
基金supported by grants from the National Natural Science Foundation of China(Grant numbers 81920108004 and 82270127)the Fundamental Research Funds of the Central Universities of Central South University(Grant number 2021zzts0562)the Fundamental Research Funds for the Scientific Research Innovation Project of Hunan Province(Grant number CX20210182).
文摘Erythropoiesis is a complex,precise,and lifelong process that is essential for maintaining normal body functions.Its strict regulation is necessary to prevent a variety of blood diseases.Normal erythropoiesis is precisely regulated by an intricate network that involves transcription levels,signal transduction,and various epigenetic modifications.In recent years,research on posttranscriptional levels in erythropoiesis has expanded significantly.The dynamic regulation of splicing transitions is responsible for changes in protein isoform expression that add new functions beneficial for erythropoiesis.RNA-binding proteins adapt the translation of transcripts to the protein requirements of the cell,yielding mRNA with dynamic translation efficiency.Noncoding RNAs,such as microRNAs and lncRNAs,are indispensable for changing the translational efficiency and/or stability of targeted mRNAs to maintain the normal expression of genes related to erythropoiesis.N6-methyladenosine-dependent regulation of mRNA translation plays an important role in maintaining the expression programs of erythroid-related genes and promoting erythroid lineage determination.This review aims to describe our current understanding of the role of post-transcriptional regulation in erythropoiesis and erythroid-associated diseases,and to shed light on the physiological and pathological implications of the post-transcriptional regulation machinery in erythropoiesis.These may help to further enrich our understanding of the regulatory network of erythropoiesis and provide new strategies for the diagnosis and treatment of erythroid-related diseases.
基金supported by the National Key Research and Development Program of China(2016YFA0102300 and 2017YFA0103102)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-002,2016-I2M-1-018 and 2017-I2M-1-015)+3 种基金National Natural Science Foundation of China(81870089 and 81700105)CAMS Medical Epigenetics Research Center(2018PT31033)Supported by the Fundamental Research Funds for the Central Universities(3332018157)State Key Laboratory of Experimental Hematology Research Grant(157-z18-07).
文摘The transcription of essentially the entire eukaryotic genome produces a huge amount of non-coding RNAs.Among them,long noncoding RNAs(lncRNAs)consist of a significant portion that widely exists across mammal genome,generating from high-throughput transcriptomic studies in the last decade.Although the functions of most lncRNAs remain to be further investigated,many of them have already been shown to play critical roles during normal development and disease conditions.Increasing evidence indicates that lncRNAs involve in versatile biological processes during erythroid proliferation and differentiation,including erythroid cell survival,heme metabolism,globin switching and regulation,erythroid enucleation,etc,via cis-or trans-mediated molecular mechanisms.In this review,we focus on recent advances regarding the functions and mechanisms of lncRNAs in normal erythropoiesis.
文摘BACKGROUND： Erythropoiesis is regulated by a range of intrinsic and extrinsic factors, including different cytokines. Recently, the role of catecholamines has been highlighted in the development of erythroid cell lineages. OBJECTIVE： This study focuses on the biological links interconnecting erythroid development and the sympathetic nervous system. The emerging evidence that underscores the role of catecholamines in the regulation of erythropoietin and other erythropoiesis cytokines are thoroughly reviewed, in addition to elements such as iron and the leptin hormone that are involved in erythropoiesis. METHODS： Relevant English-language studies were identified and retrieved from the PubMed search engine （1981-2017） using the following keywords： ＂Erythropoiesis＂, ＂Catecholamines＂, ＂Nervous system＂, and ＂Cytokines.＂ RESULTS： Chronic social stress alters and suppresses erythroid development. However, the physiological release of catecholamines is an additional stimulator of erythropoiesis in the setting of anemia. Therefore, the severity and timing of catecholamine secretion might distinctly regulate erythroid homeostasis. CONCLUSION： Understanding the relationship of catecholamines with different elements of the erythroid islands will be essential to find the tightly regulated production of red blood cells （RBCs） in both chronic and physiological catecholamine activation.
基金supported by the Science and Technology Research Project of Henan(Grant No.232102311003)the National Natural Science Foundation of China(Grant No.U1804282)。
文摘The fetal liver(FL)is the key erythropoietic organ during fetal development,but knowledge on human FL erythropoiesis is very limited.In this study,we sorted primary erythroblasts from FL cells and performed RNA sequencing(RNA-seq)analyses.We found that temporal gene expression patterns reflected changes in function during primary human FL terminal erythropoiesis.Notably,the expression of genes enriched in proteolysis and autophagy was up-regulated in orthochromatic erythroblasts(OrthoEs),suggesting the involvement of these pathways in enucleation.We also performed RNA-seq of in vitro cultured erythroblasts derived from FL CD34+cells.Comparison of transcriptomes between the primary and cultured erythroblasts revealed significant differences,indicating impacts of the culture system on gene expression.Notably,the expression of lipid metabolism-related genes was increased in cultured erythroblasts.We further immortalized erythroid cell lines from FL and cord blood(CB)CD34+cells(FL-iEry and CB-iEry,respectively).FL-iEry and CB-iEry were immortalized at the proerythroblast stage and can be induced to differentiate into OrthoEs,but their enucleation ability was very low.Comparison of the transcriptomes between OrthoEs with and without enucleation capability revealed the down-regulation of pathways involved in chromatin organization and mitophagy in OrthoEs without enucleation capacity,indicating that defects in chromatin organization and mitophagy contribute to the inability of OrthoEs to enucleate.Additionally,the expression of HBE1,HBZ,and HBG2 was up-regulated in FL-iEry compared with CB-iEry,and such up-regulation was accompanied by down-regulated expression of BCL11A and up-regulated expression of LIN28B and IGF2BP1.Our study provides new insights into human FL erythropoiesis and rich resources for future studies.
文摘MicroRNAs （miRNAs） are 19-24 nucleotide non-coding ribonucleic acids binding DNA or RNA and controlling gene expression via mRNA degradation or its transcription inhibition. Erythropoies is a multi step differentiation process of erythroid progenitors to nucleate red blood cells. Maturation, proliferation and differentiation of red blood cells is affected by erythroid factors, signaling pathways in niche of hematopoietic cells, transcription factors as well as miRNAs. Expression of different types of miRNAs during erythroid development provides a background for the study of these molecules to control erythroid differentiation and maturation as well as their use as diagnostic and prognostic markers to treat erythroid disorders like thalassemia, sickle cell disease and erythrocyte enzyme deficiencies. In this paper, with reference to biosynthesis of miRNAs, their function in normal and anemic erythropoiesis has been investigated. The target molecule of each of these miRNAs has been cited in an attempt to elucidate their role in erythropoiesis.
文摘Anemia,usually due to iron deficiency,is highly prevalent among patients with colorectal cancer.Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization.Preoperative anemia predicts for decreased survival.Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes,increased post-operative nosocomial infections,longer hospital stays,increased rates of cancer recurrence and perioperative venous thromboembolism.Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management,minimizes or eliminates allogeneic blood transfusion.This includes restrictive transfusion policy,thromboprophylaxis and anemia management to improve outcomes.Normalization of preoperative hemoglobin levels is a World Health Organization recommendation.Iron repletion should be routinely ordered when indicated.Oral iron is poorly tolerated with low adherence based on published evidence.Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions.Serious adverse events with intravenous iron are extremely rare.Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care.Erythropoiesis stimulating agents may improve response rates.A multidisciplinary,multimodal,individualized strategy,collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.
基金Supported by Ministry of University and Research, FIRB 2003 to APAssociation for the Study of Hemochromatosis and Iron Overload Diseases, Monza, to PT and RM+1 种基金Telethon Italy (n° GGP06213)the Cariverona Foundation, Verona, Italy to DG
文摘By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.
