The single cell isolation technique was used to detect fetal nucleated erythroblasts at a single cell level from the peripheral blood of pregnant women in order to investigate the feasibility of this method for nonin...The single cell isolation technique was used to detect fetal nucleated erythroblasts at a single cell level from the peripheral blood of pregnant women in order to investigate the feasibility of this method for noninvasive prenatal diagnosis. Single fetal nucleated erythroblasts were isolated from the peripheral blood samples from 51 pregnant women by micromanipulation techniques after density gradient centrifugation. Nested polymerase chain reaction method was used to amplify the SRY gene. It was found that the concordance rate of amplification results with real fetal sex was 82.61 %. The sensitivity and specificity were 80 % and 87.50 % respectively. It was suggested that it is feasible and promising in non invasive prenatal diagnosis to detect fetal nucleated erythroblasts at a single cell level by using micromanipulation techniques.展开更多
The erythroblastic island(EBI)is a multicellular structure defined by the presence of 1 or 2 central macrophages surrounded by at least 3 erythroblasts.EBIs were initially proposed as a specialized microenvironment ex...The erythroblastic island(EBI)is a multicellular structure defined by the presence of 1 or 2 central macrophages surrounded by at least 3 erythroblasts.EBIs were initially proposed as a specialized microenvironment exclusively for erythroid terminal differentiation.Recent advancements in techniques such as lineage tracing mouse models,imaging flow cytometry,and single-cell RNA sequencing,accumulating evidence has provided novel insights that challenge this conventional view.Notably,the erythropoietin receptor has been identified as a novel marker for EBI macrophages.Additionally,neutrophils have been identified as novel cellular components of EBIs,raising the intriguing hypothesis that EBIs may support other hematopoietic lineage cells as well.Beyond the diverse cellular components of various hematopoietic lineages,even within the erythroid lineage,an immune-prone erythroblast subpopulation has been reported,although it remains unclear whether and how these immune-prone erythroblasts mature in EBIs.These observations indicate that EBIs are a heterogeneous population.In this review,we summarize the most recent findings on EBIs,discuss their potential immune functions,and provide a perspective for future investigations.展开更多
Erythroblastic island(EBI),composed of a central macrophage surrounded by developing erythroid cells,is a structure found in hematopoietic tissues such as fetal liver and bone marrow.It is the first described hematopo...Erythroblastic island(EBI),composed of a central macrophage surrounded by developing erythroid cells,is a structure found in hematopoietic tissues such as fetal liver and bone marrow.It is the first described hematopoietic niche that predominantly supports erythropoiesis.Although it is well accepted that EBIs and EBI macrophage play important roles during erythropoiesis,the mechanisms by which they support erythropoiesis remain largely unclear due to our inability to identify and isolate EBI macrophages.Earlier efforts to identify surface markers for EBI macrophages have focused on the adhesion molecules which are involved in macrophage’s interaction with erythroblasts.These include EMP,Vcam1,CD169,CD163,and aV integrin.Findings from these earlier studies suggested that combination of Vcam1,CD169,and mouse macrophage surface marker F4/80 can be used to define mouse EBI macrophage.We found that not all F4/80+Vcam1+CD169+macrophages are EBI macrophages.Instead,we discovered that EBI macrophages are characterized by the expression of Epor in both mouse and man.RNA-seq analyses of the newly identified EBI macrophages revealed that EBI macrophages have involved specialized function in supporting erythropoiesis.Our findings provide foundation for future studies.Here we will review current knowledge of EBI macrophages and discuss future perspectives.展开更多
The aryl hydrocarbon receptor(AHR)plays an important role during mammalian embryo development.Inhibition of AHR signaling promotes the development of hematopoietic stem/progenitor cells.AHR also regulates the function...The aryl hydrocarbon receptor(AHR)plays an important role during mammalian embryo development.Inhibition of AHR signaling promotes the development of hematopoietic stem/progenitor cells.AHR also regulates the functional maturation of blood cells,such as T cells and megakaryocytes.However,little is known about the role of AHR modulation during the development of erythroid cells.In this study,we used the AHR antagonist StemRegenin 1(SR1)and the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin during different stages of human erythropoiesis to elucidate the function of AHR.We found that antagonizing AHR signaling improved the production of human embryonic stem cell derived erythrocytes and enhanced erythroid terminal differentiation.RNA sequencing showed that SR1 treatment of proerythroblasts upregulated the expression of erythrocyte differentiation-related genes and downregulated actin organization-associated genes.We found that SR1 accelerated F-actin remodeling in terminally differentiated erythrocytes,favoring their maturation of the cytoskeleton and enucleation.We demonstrated that the effects of AHR inhibition on erythroid maturation were associated with F-actin remodeling.Our findings help uncover the mechanism for AHRmediated human erythroid cell differentiation.We also provide a new approach toward the large-scale production of functionally mature human pluripotent stem cell-derived erythrocytes for use in translational applications.展开更多
The post-transcriptional regulation of mRNA is a crucial component of gene expression.The disruption of this process has detrimental effects on the normal development and gives rise to various diseases.Searching for n...The post-transcriptional regulation of mRNA is a crucial component of gene expression.The disruption of this process has detrimental effects on the normal development and gives rise to various diseases.Searching for novel post-transcriptional regulators and exploring their roles are essential for understanding development and disease.Through a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell development.FAM46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroidspecific enhancer.We demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent manner.Furthermore,we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis.In conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.展开更多
基金This project was supported by a grant from Science Foun-dation of Ministry of Public Heath of China (No. 96 .2 - 112 )and a grant from Hubei Provincial National Natural ScienceFoundation(96 J0 6 8)
文摘The single cell isolation technique was used to detect fetal nucleated erythroblasts at a single cell level from the peripheral blood of pregnant women in order to investigate the feasibility of this method for noninvasive prenatal diagnosis. Single fetal nucleated erythroblasts were isolated from the peripheral blood samples from 51 pregnant women by micromanipulation techniques after density gradient centrifugation. Nested polymerase chain reaction method was used to amplify the SRY gene. It was found that the concordance rate of amplification results with real fetal sex was 82.61 %. The sensitivity and specificity were 80 % and 87.50 % respectively. It was suggested that it is feasible and promising in non invasive prenatal diagnosis to detect fetal nucleated erythroblasts at a single cell level by using micromanipulation techniques.
基金supported by grants from the National Key Research and Development Program of China(2022YFA1103503 to L.S.,2024YFC2510500 to J.G.)the National Natural Science Foundation of China(82225003 to L.S.,82100152 to J.T.,U24A20749 to J.T.,82300141 to J.G.,82400148 to J.M.)+2 种基金the CAMS Innovation Fund for Medical Sciences(2023-I2M-2-007 to L.S.,2021-I2M-1-040 to L.S.,2021-I2M-1-073 to J.T.,2024-I2M-TS-036 to L.S.)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH24KYZX0005 to L.S.)Tianjin Municipal Science and Technology Commission Grant(24ZXRKSY00010 to L.S.,24ZXZSSS00080 to J.T.,23ZXRKSY00010 to L.S.).
文摘The erythroblastic island(EBI)is a multicellular structure defined by the presence of 1 or 2 central macrophages surrounded by at least 3 erythroblasts.EBIs were initially proposed as a specialized microenvironment exclusively for erythroid terminal differentiation.Recent advancements in techniques such as lineage tracing mouse models,imaging flow cytometry,and single-cell RNA sequencing,accumulating evidence has provided novel insights that challenge this conventional view.Notably,the erythropoietin receptor has been identified as a novel marker for EBI macrophages.Additionally,neutrophils have been identified as novel cellular components of EBIs,raising the intriguing hypothesis that EBIs may support other hematopoietic lineage cells as well.Beyond the diverse cellular components of various hematopoietic lineages,even within the erythroid lineage,an immune-prone erythroblast subpopulation has been reported,although it remains unclear whether and how these immune-prone erythroblasts mature in EBIs.These observations indicate that EBIs are a heterogeneous population.In this review,we summarize the most recent findings on EBIs,discuss their potential immune functions,and provide a perspective for future investigations.
文摘Erythroblastic island(EBI),composed of a central macrophage surrounded by developing erythroid cells,is a structure found in hematopoietic tissues such as fetal liver and bone marrow.It is the first described hematopoietic niche that predominantly supports erythropoiesis.Although it is well accepted that EBIs and EBI macrophage play important roles during erythropoiesis,the mechanisms by which they support erythropoiesis remain largely unclear due to our inability to identify and isolate EBI macrophages.Earlier efforts to identify surface markers for EBI macrophages have focused on the adhesion molecules which are involved in macrophage’s interaction with erythroblasts.These include EMP,Vcam1,CD169,CD163,and aV integrin.Findings from these earlier studies suggested that combination of Vcam1,CD169,and mouse macrophage surface marker F4/80 can be used to define mouse EBI macrophage.We found that not all F4/80+Vcam1+CD169+macrophages are EBI macrophages.Instead,we discovered that EBI macrophages are characterized by the expression of Epor in both mouse and man.RNA-seq analyses of the newly identified EBI macrophages revealed that EBI macrophages have involved specialized function in supporting erythropoiesis.Our findings provide foundation for future studies.Here we will review current knowledge of EBI macrophages and discuss future perspectives.
基金supported by the National Basic Research Program(973 Program,2015CB964902)the National Natural Science Foundation of China(H81170466 and H81370597)the CAMS Initiatives for Innovative Medicine(2016-I2M-1-018,2019-I2M-1-006,and 2017-I2M-2005)to F.M.,the National Natural Science Foundation of China Youth Fund(82000119)to Yonggang Zhang.
文摘The aryl hydrocarbon receptor(AHR)plays an important role during mammalian embryo development.Inhibition of AHR signaling promotes the development of hematopoietic stem/progenitor cells.AHR also regulates the functional maturation of blood cells,such as T cells and megakaryocytes.However,little is known about the role of AHR modulation during the development of erythroid cells.In this study,we used the AHR antagonist StemRegenin 1(SR1)and the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin during different stages of human erythropoiesis to elucidate the function of AHR.We found that antagonizing AHR signaling improved the production of human embryonic stem cell derived erythrocytes and enhanced erythroid terminal differentiation.RNA sequencing showed that SR1 treatment of proerythroblasts upregulated the expression of erythrocyte differentiation-related genes and downregulated actin organization-associated genes.We found that SR1 accelerated F-actin remodeling in terminally differentiated erythrocytes,favoring their maturation of the cytoskeleton and enucleation.We demonstrated that the effects of AHR inhibition on erythroid maturation were associated with F-actin remodeling.Our findings help uncover the mechanism for AHRmediated human erythroid cell differentiation.We also provide a new approach toward the large-scale production of functionally mature human pluripotent stem cell-derived erythrocytes for use in translational applications.
基金funded by the Starting Fund from Zhejiang University to N.L.and grants to X.L.from National Natural Science Foundation of China(82170120 and 81670108)CAMS Initiative for Innovative Medicine(2017-12M-B&R-04)+2 种基金Medical Epigenetics Research Cen-ter,CAMS(2018PT31015)the State Key Laboratory of Medical Molecular Biology(2060204)Haihe L aboratory of Cell Ecosystem Innovation Fund(22HHXBSS00008).
文摘The post-transcriptional regulation of mRNA is a crucial component of gene expression.The disruption of this process has detrimental effects on the normal development and gives rise to various diseases.Searching for novel post-transcriptional regulators and exploring their roles are essential for understanding development and disease.Through a multimodal analysis of red blood cell trait genome-wide association studies(GWAS)and transcriptomes of erythropoiesis,we identify FAM46C,a non-canonical RNA poly(A)polymerase,as a necessary factor for proper red blood cell development.FAM46C is highly expressed in the late stages of the erythroid lineage,and its developmental upregulation is controlled by an erythroidspecific enhancer.We demonstrate that FAM46C stabilizes mRNA and regulates erythroid differentiation in a polymerase activity-dependent manner.Furthermore,we identify transcripts of lysosome and mitochondria components as highly confident in vivo targets of FAM46C,which aligns with the need of maturing red blood cells for substantial clearance of organelles and maintenance of cellular redox homeostasis.In conclusion,our study unveils a unique role of FAM46C in positively regulating lysosome and mitochondria components,thereby promoting erythropoiesis.
