Sperm is essential for successful artificial insemination in dairy cattle,and its quality can be influenced by both epi-genetic modification and epigenetic inheritance.The bovine germline differentiation is characteri...Sperm is essential for successful artificial insemination in dairy cattle,and its quality can be influenced by both epi-genetic modification and epigenetic inheritance.The bovine germline differentiation is characterized by epigenetic reprogramming,while intergenerational and transgenerational epigenetic inheritance can influence the offspring’s development through the transmission of epigenetic features to the offspring via the germline.Therefore,the selec-tion of bulls with superior sperm quality for the production and fertility traits requires a better understanding of the epigenetic mechanism and more accurate identifications of epigenetic biomarkers.We have comprehensively reviewed the current progress in the studies of bovine sperm epigenome in terms of both resources and biological discovery in order to provide perspectives on how to harness this valuable information for genetic improvement in the cattle breeding industry.展开更多
Immunotherapy is currently one of the most promising treatment options for malignant melanoma[1].To uncover new immunological targets for future treatment approaches,single-cell transcriptomic and epigenomic analyses ...Immunotherapy is currently one of the most promising treatment options for malignant melanoma[1].To uncover new immunological targets for future treatment approaches,single-cell transcriptomic and epigenomic analyses were performed on human primary melanoma(MM)and melanocytic nevus(Nev)samples(Figure 1A).展开更多
Biodiversity is facing unprecedented challenges due to rapidly changing environments. While genetic and genomic tools have revolutionized conservation biology by enabling scientists to reconstruct evolutionary histori...Biodiversity is facing unprecedented challenges due to rapidly changing environments. While genetic and genomic tools have revolutionized conservation biology by enabling scientists to reconstruct evolutionary histories, delineate population structures, and assess adaptive potential of threatened species(Hu et al., 2024), they often fall short in addressing the urgency of environmental threats.展开更多
The meticulous examination of the genomic,transcriptomic,epigenomic,and proteomic landscapes,conducted at the precise resolution of single cells,has emerged as an indispensable instrument for comprehending the inheren...The meticulous examination of the genomic,transcriptomic,epigenomic,and proteomic landscapes,conducted at the precise resolution of single cells,has emerged as an indispensable instrument for comprehending the inherent mechanisms governing cellular heterogeneity.These methodologies have provided unprecedented insights into the intrinsic and extrinsic factors that underlie cellular morphological characteristics and differentiated functions.Within this field,multimodal techniques that concurrently analyze the epigenetic features of chromatin or cellular proteins and gene expression within an identical cell delineate intricate gene regulatory networks and phenotypes,thereby enhancing our understanding of cellular states during differentiation or pathological conditions.These techniques can be applied to identify cell subpopulations,infer cell developmental trajectories,and analyze patterns of cell-to-cell communication.In this context,we initiate by delineating the singular cell separation techniques employed in single-cell multiomics.Subsequently,we narrow our focus to methodologies amalgamating epigenetic features with gene expression at single-cell resolution.The epigenetic features entail DNA methylation,chromatin accessibility,histone modifications,chromatin conformation,and transcription factors.Following this,we discuss techniques for the conjoint analysis of cell surface and intracellular proteins in tandem with the transcriptome.Finally,we discuss the challenges and opportunities that manifest within this field,contributing to its continued advancement and exploration.展开更多
Colorectal cancer(CRC)is a common malignant tumor with a high mortality rate worldwide.Advanced CRC often leads to liver metastasis,which has a poor prognosis,highlighting the need to investigate the underlying mechan...Colorectal cancer(CRC)is a common malignant tumor with a high mortality rate worldwide.Advanced CRC often leads to liver metastasis,which has a poor prognosis,highlighting the need to investigate the underlying mechanisms.Omics,encompassing genomics,epigenomics,transcriptomics,proteomics,metabolomics,and microbiomics,enables comprehensive molecular analysis of cells and tissues.Tumor-omics research has advanced rapidly,with growing attention on CRC-related omics.However,systematic reviews on omics research specific to colorectal cancer liver metastasis(CRLM)are limited.This review summarizes the current status and progress of multi-omics research on CRLM and discusses the application of multi-omics technologies in basic research and the significant clinical implications.展开更多
DNA methylation is a key chromatin modification in plant genomes that is meiotically and mitotically her- itable, and at times is associated with gene expression and morphological variation. Benefiting from the increa...DNA methylation is a key chromatin modification in plant genomes that is meiotically and mitotically her- itable, and at times is associated with gene expression and morphological variation. Benefiting from the increased availability of high-quality reference genome assemblies and methods to profile single-base res- olution DNA methylation states, DNA methylomes for many crop species are available. These efforts are making it possible to begin answering crucial questions, including understanding the role of DNA methyl- ation in developmental processes, its role in crop species evolution, and whether DNA methylation is dynamically altered and heritable in response to changes in the environment. These genome-wide maps provide evidence for the existence of silent epialleles in plant genomes which, once identified, can be tar- geted for reactivation leading to phenotypic variation.展开更多
Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional bree...Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.展开更多
BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders...BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of P<0.001.The test group also significantly increased their consumption of whole and/or organic foods with a pre-intervention diet score of 100(mean=5.882,SD=2.472)and post-intervention diet score of 121(mean=7.118,SD=2.390)and the paired t-test analysis showing a significance of P<0.05.CONCLUSION Here we show nutritional epigenetics education can be used to reduce ultra-processed food intake and improve attitude among parents having learning-disabled children with autism or ADHD.展开更多
Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epst...Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.展开更多
BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical valu...BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.展开更多
Cholestatic liver diseases(CLD)begin to develop after an impairment of bile flow start to affect the biliary tree.Cholangiocytes actively participate in the liver response to injury and repair and the intensity of thi...Cholestatic liver diseases(CLD)begin to develop after an impairment of bile flow start to affect the biliary tree.Cholangiocytes actively participate in the liver response to injury and repair and the intensity of this reaction is a determinant factor for the development of CLD.Progressive cholangiopathies may ultimately lead to end-stage liver disease requiring at the end orthotopic liver transplantation.This narrative review will discuss cholangiocyte biology and pathogenesis mechanisms involved in four intrahepatic CLD:Primary biliary cholangitis,primary sclerosing cholangitis,cystic fibrosis involving the liver,and polycystic liver disease.展开更多
AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension(EH), and to further elucidate their role in EH. METHODS: We searched for genetic and epigenetic factors in major s...AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension(EH), and to further elucidate their role in EH. METHODS: We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online re-source. We found 11 genome wide association studies(GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or nega-tive effects, as this article is only meant to be a sum-mary of genes associated with any aspect of EH.RESULTS: We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes withmultiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA tar-gets found to be associated with EH, many of the genes involved were also identified in the GWAS studies.CONCLUSION: Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequenc-ing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discov-ered creating a tremendous potential for personalized medicine using pharmacogenomics.展开更多
SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer （PCa） tissues and cells and to preliminarily investigate the ...SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer （PCa） tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry （IHC） were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia （BPH） tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced GO/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDBt which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.展开更多
Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture...Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.展开更多
Epigenomes including genome-wide histone modification and DNA methylation profiles are important for genome activity and fof defining gene expression patterns of plant development and responses to various environmenta...Epigenomes including genome-wide histone modification and DNA methylation profiles are important for genome activity and fof defining gene expression patterns of plant development and responses to various environmental conditions. Rice is the most important crop plant and serves as a model for cereal genomics. Rice epigenomic landscape is emerging and the function of chromatin modification regulators in gene expression, transposon repression and plant development is being characterized. Epigenomic variation that gives rise to stable or transgenerational heritable epialleles related to variation of important agronomical traits or stress responses is being characterized in rice. Implication of epigenomic variation in rice heterosis is being exploited.展开更多
Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oe...Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors(ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growthpromoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors(p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high(> 10) μmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability toinhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of "free" unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.展开更多
Lymphomas enconlpass a group of malignancies that originate in the lymph nodes or other lymphoid tissues. Epigenetic modification, especially by histone deacetylase （HDACs）, plays a key role during the occurrence an...Lymphomas enconlpass a group of malignancies that originate in the lymph nodes or other lymphoid tissues. Epigenetic modification, especially by histone deacetylase （HDACs）, plays a key role during the occurrence and development of lymphomas. Consequently, HDAC inhibitors （HDACIs）, a class of gene expression-modulating drugs, have emerged as promising mechanism-based agents for the treatment of lymphomas. This review presents the rationale of HDAC inhibition, describes the epigenetic-based mechanisms of action of HDACIs, discusses their clinical efficiency, and summarizes the current and future developments in this field.展开更多
The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-d...The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine—first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that（i） there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives;（ii） first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and（iii） maternal age at birth of the maxillary canine—first premolar transposition probands was significantly higher than that of the palatally displaced canine probands.The results suggest that maxillary canine—first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development.展开更多
Psychiatric disorders,including suicide,are complex disorders that are affected by many different risk factors.It has been estimated that genetic factors contribute up to 50%to suicide risk.As the candidate gene appro...Psychiatric disorders,including suicide,are complex disorders that are affected by many different risk factors.It has been estimated that genetic factors contribute up to 50%to suicide risk.As the candidate gene approach has not identified a gene or set of genes that can be defined as biomarkers for suicidal behaviour,much is expected from cutting edge technological approaches that can interrogate several hundred,or even millions,of biomarkers at a time.These include the‘-omic’approaches,such as genomics,transcriptomics,epigenomics,proteomics and metabolomics.Indeed,these have revealed new candidate biomarkers associated with suicidal behaviour.The most interesting of these have been implicated in inflammation and immune responses,which have been revealed through different study approaches,from genome-wide single nucleotide studies and the micro-RNA transcriptome,to the proteome and metabolome.However,the massive amounts of data that are generated by the‘-omic’technologies demand the use of powerful computational analysis,and also specifically trained personnel.In this regard,machine learning approaches are beginning to pave the way towards personalized psychiatry.展开更多
Intensively developed in the last few years, single-cell sequencing technologies now present numerous advantages over traditional sequencing methods for solving the problems of biological heterogeneity and low quantit...Intensively developed in the last few years, single-cell sequencing technologies now present numerous advantages over traditional sequencing methods for solving the problems of biological heterogeneity and low quantities of available biological materials. The application of single-cell sequencing technologies has profoundly changed our understanding of a series of biological phenomena, including gene transcription, embryo development, and carcinogenesis. However, before single-cell sequencing technologies can be used extensively, researchers face the serious challenge of overcoming inherent issues of high amplification bias, low accuracy and repro- ducibility. Here, we simply summarize the techniques used for single-cell isolation, and review the current technologies used in single-cell genomic, transcriptomic, and epigenomic sequencing, We discuss the merits, defects, and scope of application of single-cell sequencing technologies and then speculate on the direction of future developments.展开更多
基金funded by the National Key R&D Program of China(2021YFD1200903)Seed Fund(CAU),Shandong Provincial Natural Science Foundation(ZR2021MC070)+3 种基金the National Key R&D Program of China(2021YFF1000701-06)Shandong Provincial Natural Science Foundation(ZR2020MC165)the Earmarked Fund for CARS-36.X.W.is funded by the“Hundred Talents Program”project of Hebei Province(E2020100019)the research project of Zhongnongtongchuang(ZNTC)group(ZNTC2019A10 and ZNTC2021B12)in China.
文摘Sperm is essential for successful artificial insemination in dairy cattle,and its quality can be influenced by both epi-genetic modification and epigenetic inheritance.The bovine germline differentiation is characterized by epigenetic reprogramming,while intergenerational and transgenerational epigenetic inheritance can influence the offspring’s development through the transmission of epigenetic features to the offspring via the germline.Therefore,the selec-tion of bulls with superior sperm quality for the production and fertility traits requires a better understanding of the epigenetic mechanism and more accurate identifications of epigenetic biomarkers.We have comprehensively reviewed the current progress in the studies of bovine sperm epigenome in terms of both resources and biological discovery in order to provide perspectives on how to harness this valuable information for genetic improvement in the cattle breeding industry.
基金supported by the Deutsche Forschungsgemeinschaft(DFG)(German Research Foundation,grant numbers:KU 1320/10-1 and HO 6586/1-1,and SFB1430,project 424228829)the Sachsische Aufbaubank(grant number:10071450).
文摘Immunotherapy is currently one of the most promising treatment options for malignant melanoma[1].To uncover new immunological targets for future treatment approaches,single-cell transcriptomic and epigenomic analyses were performed on human primary melanoma(MM)and melanocytic nevus(Nev)samples(Figure 1A).
基金supported by Major Program of the Natural Science Foundation of Jiangxi Province of China (20233ACB209001)Young Elite Scientists Sponsorship Program by CAST (2023QNRC001)+3 种基金Young Scientists Fund of the National Natural Science Foundation of China (32400346)Science and Technology Department of Guangdong Province (2023A1111110001)Guangdong Forestry Administration (SLYJ2023B4004)PI Project of Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)(GML2020GD0804, GML2022GD0804)。
文摘Biodiversity is facing unprecedented challenges due to rapidly changing environments. While genetic and genomic tools have revolutionized conservation biology by enabling scientists to reconstruct evolutionary histories, delineate population structures, and assess adaptive potential of threatened species(Hu et al., 2024), they often fall short in addressing the urgency of environmental threats.
基金supported by the National Natural Science Foundation of China(92253202 and 22177087 to X.W.)the Ministry of Science and Technology(2023YFC3402200)the Fundamental Research Funds for the Central Universities(2042023kfyq05).
文摘The meticulous examination of the genomic,transcriptomic,epigenomic,and proteomic landscapes,conducted at the precise resolution of single cells,has emerged as an indispensable instrument for comprehending the inherent mechanisms governing cellular heterogeneity.These methodologies have provided unprecedented insights into the intrinsic and extrinsic factors that underlie cellular morphological characteristics and differentiated functions.Within this field,multimodal techniques that concurrently analyze the epigenetic features of chromatin or cellular proteins and gene expression within an identical cell delineate intricate gene regulatory networks and phenotypes,thereby enhancing our understanding of cellular states during differentiation or pathological conditions.These techniques can be applied to identify cell subpopulations,infer cell developmental trajectories,and analyze patterns of cell-to-cell communication.In this context,we initiate by delineating the singular cell separation techniques employed in single-cell multiomics.Subsequently,we narrow our focus to methodologies amalgamating epigenetic features with gene expression at single-cell resolution.The epigenetic features entail DNA methylation,chromatin accessibility,histone modifications,chromatin conformation,and transcription factors.Following this,we discuss techniques for the conjoint analysis of cell surface and intracellular proteins in tandem with the transcriptome.Finally,we discuss the challenges and opportunities that manifest within this field,contributing to its continued advancement and exploration.
基金supported by grants from the Natural Science Foundation of Chongqing(Grant No.CSTB2024NSCQ-MSX0478).
文摘Colorectal cancer(CRC)is a common malignant tumor with a high mortality rate worldwide.Advanced CRC often leads to liver metastasis,which has a poor prognosis,highlighting the need to investigate the underlying mechanisms.Omics,encompassing genomics,epigenomics,transcriptomics,proteomics,metabolomics,and microbiomics,enables comprehensive molecular analysis of cells and tissues.Tumor-omics research has advanced rapidly,with growing attention on CRC-related omics.However,systematic reviews on omics research specific to colorectal cancer liver metastasis(CRLM)are limited.This review summarizes the current status and progress of multi-omics research on CRLM and discusses the application of multi-omics technologies in basic research and the significant clinical implications.
文摘DNA methylation is a key chromatin modification in plant genomes that is meiotically and mitotically her- itable, and at times is associated with gene expression and morphological variation. Benefiting from the increased availability of high-quality reference genome assemblies and methods to profile single-base res- olution DNA methylation states, DNA methylomes for many crop species are available. These efforts are making it possible to begin answering crucial questions, including understanding the role of DNA methyl- ation in developmental processes, its role in crop species evolution, and whether DNA methylation is dynamically altered and heritable in response to changes in the environment. These genome-wide maps provide evidence for the existence of silent epialleles in plant genomes which, once identified, can be tar- geted for reactivation leading to phenotypic variation.
基金supported by funding from the National Key R&D Program of China(2023ZD0407304)the Sci-Tech Innovation 2030 Agenda(2022ZD0115703)Fundamental Research Funds for Central Non-Profit of Chinese Academy of Agricultural Sciences(Y2023PT20).
文摘Epigenetics-mediated breeding(epibreeding)involves engineering crop traits and stress responses through the targeted manipulation of key epigenetic features to enhance agricultural productivity.While conventional breeding methods raise concerns about reduced genetic diversity,epibreeding propels crop improvement through epigenetic variations that regulate gene expression,ultimately impacting crop yield.Epigenetic regulation in crops encompasses various modes,including histone modification,DNA modification,RNA modification,non-coding RNA,and chromatin remodeling.This review summarizes the epigenetic mechanisms underlying major agronomic traits in maize and identifies candidate epigenetic landmarks in the maize breeding process.We propose a valuable strategy for improving maize yield through epibreeding,combining CRISPR/Cas-based epigenome editing technology and Synthetic Epigenetics(SynEpi).Finally,we discuss the challenges and opportunities associated with maize trait improvement through epibreeding.
文摘BACKGROUND Unhealthy maternal diet leads to heavy metal exposures from the consumption of ultra-processed foods that may impact gene behavior across generations,creating conditions for the neurodevelopmental disorders known as autism and attention deficit/hyperactivity disorder(ADHD).Children with these disorders have difficulty metabolizing and excreting heavy metals from their bloodstream,and the severity of their symptoms correlates with the heavy metal levels measured in their blood.Psychiatrists may play a key role in helping parents reduce their ultra-processed food and dietary heavy metal intake by providing access to effective nutritional epigenetics education.AIM To test the efficacy of nutritional epigenetics instruction in reducing parental ultra-processed food intake.METHODS The study utilized a semi-randomized test and control group pretest-posttest pilot study design with participants recruited from parents having a learning-disabled child with autism or ADHD.Twenty-two parents who met the inclusion criteria were randomly selected to serve in the test(n=11)or control(n=11)group.The test group participated in the six-week online nutritional epigenetics tutorial,while the control group did not.The efficacy of the nutritional epigenetics instruction was determined by measuring changes in parent diet and attitude using data derived from an online diet survey administered to the participants during the pre and post intervention periods.Diet intake scores were derived for both ultra-processed and whole/organic foods.Paired sample t-tests were conducted to determine any differences in mean diet scores within each group.RESULTS There was a significant difference in the diet scores of the test group between the pre-and post-intervention periods.The parents in the test group significantly reduced their intake of ultra-processed foods with a preintervention diet score of 70(mean=5.385,SD=2.534)and a post-intervention diet score of 113(mean=8.692,SD=1.750)and the paired t-test analysis showing a significance of P<0.001.The test group also significantly increased their consumption of whole and/or organic foods with a pre-intervention diet score of 100(mean=5.882,SD=2.472)and post-intervention diet score of 121(mean=7.118,SD=2.390)and the paired t-test analysis showing a significance of P<0.05.CONCLUSION Here we show nutritional epigenetics education can be used to reduce ultra-processed food intake and improve attitude among parents having learning-disabled children with autism or ADHD.
文摘Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.
基金the National Natural Science Foundation of China,No.81960504the“Xingdian Talents”Support Project of Yunnan Province,No.RLQB20200002+2 种基金the Medical Discipline Reserve Talents of Yunnan Province,No.H-2018015the Applied Basic Research Projects-Union Foundation of Kunming Medical University,No.2017FE467(-132)the Talent Introduction Project of Hubei Polytechnic University,No.21xjz34R。
文摘BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.
文摘Cholestatic liver diseases(CLD)begin to develop after an impairment of bile flow start to affect the biliary tree.Cholangiocytes actively participate in the liver response to injury and repair and the intensity of this reaction is a determinant factor for the development of CLD.Progressive cholangiopathies may ultimately lead to end-stage liver disease requiring at the end orthotopic liver transplantation.This narrative review will discuss cholangiocyte biology and pathogenesis mechanisms involved in four intrahepatic CLD:Primary biliary cholangitis,primary sclerosing cholangitis,cystic fibrosis involving the liver,and polycystic liver disease.
文摘AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension(EH), and to further elucidate their role in EH. METHODS: We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online re-source. We found 11 genome wide association studies(GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or nega-tive effects, as this article is only meant to be a sum-mary of genes associated with any aspect of EH.RESULTS: We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes withmultiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA tar-gets found to be associated with EH, many of the genes involved were also identified in the GWAS studies.CONCLUSION: Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequenc-ing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discov-ered creating a tremendous potential for personalized medicine using pharmacogenomics.
基金This study was supported by the National Basic Research Program of China （No. 2012CB518306）, the National Natural Science Foundation of China （No. 81101946）, the Prostate Cancer Foundation Young Investigator Award and the Shanghai Pujiang Program （No. 12PID008）.
文摘SETDB1 has been established as an oncogene in a number of human carcinomas. The present study was to evaluate the expression of SETDB1 in prostate cancer （PCa） tissues and cells and to preliminarily investigate the role of SETDB1 in prostate tumorigenesis in vitro. Quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry （IHC） were used to detect the expression of SETDB1 in PCa tissues, adjacent normal tissues, benign prostatic hyperplasia （BPH） tissues, PCa cell lines and normal prostate epithelial cells. The results suggested that SETDB1 was upregulated in human PCa tissues compared with normal tissues at the mRNA and protein levels. The role of SETDB1 in proliferation was analyzed with cell counting kit-8, colony-forming efficiency and flow cytometry assays. The results indicated that downregulation of SETDB1 by siRNA inhibited PCa cell growth, and induced GO/G1 cell cycle arrest. The PCa cell migration and invasion decreased by silcencing SETDBt which were assessed by using in vitro scratch and transwell invasion assay respectively. Our data suggested that SETDB1 is overexpressed in human PCa. Silencing SETDB1 inhibited PCa cell proliferation, migration and invasion.
文摘Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.
基金supported by a grant of the Transgenic Program of the Chinese Ministry of Agriculture (No.2009ZX08009-078B)the National High-Tech R&D Program(863 Program)on rice functional genomics of the Ministry ofScience and Technology(Nos.2012AA10A303 and 2012AA10A304)supported by the program blanc CERES of the French Agence Nationale de la Recherche
文摘Epigenomes including genome-wide histone modification and DNA methylation profiles are important for genome activity and fof defining gene expression patterns of plant development and responses to various environmental conditions. Rice is the most important crop plant and serves as a model for cereal genomics. Rice epigenomic landscape is emerging and the function of chromatin modification regulators in gene expression, transposon repression and plant development is being characterized. Epigenomic variation that gives rise to stable or transgenerational heritable epialleles related to variation of important agronomical traits or stress responses is being characterized in rice. Implication of epigenomic variation in rice heterosis is being exploited.
文摘Phytoestrogens have multiple actions within target cells, including the epigenome, which could be beneficial to the development and progression of breast cancer. In this brief review the action of phytoestrogens on oestrogen receptors, cell signalling pathways, regulation of the cell cycle, apoptosis, steroid synthesis and epigenetic events in relation to breast cancer are discussed. Phytoestrogens can bind weakly to oestrogen receptors(ERs) and some have a preferential affinity for ERβ which can inhibit the transcriptional growthpromoting activity of ERα. However only saturating doses of phytoestrogens, stimulating both ERα and β, exert growth inhibitory effects. Such effects on growth may be through phytoestrogens inhibiting cell signalling pathways. Phytoestrogens have also been shown to inhibit cyclin D1 expression but increase the expression of cyclin-dependent kinase inhibitors(p21 and p27) and the tumour suppressor gene p53. Again these effects are only observed at high(> 10) μmol/L doses of phytoestrogens. Finally the effects of phytoestrogens on breast cancer may be mediated by their ability toinhibit local oestrogen synthesis and induce epigenetic changes. There are, though, difficulties in reconciling epidemiological and experimental data due to the fact experimental doses, both in vivo and in vitro, far exceed the circulating concentrations of "free" unbound phytoestrogens measured in women on a high phytoestrogen diet or those taking phytoestrogen supplements.
文摘Lymphomas enconlpass a group of malignancies that originate in the lymph nodes or other lymphoid tissues. Epigenetic modification, especially by histone deacetylase （HDACs）, plays a key role during the occurrence and development of lymphomas. Consequently, HDAC inhibitors （HDACIs）, a class of gene expression-modulating drugs, have emerged as promising mechanism-based agents for the treatment of lymphomas. This review presents the rationale of HDAC inhibition, describes the epigenetic-based mechanisms of action of HDACIs, discusses their clinical efficiency, and summarizes the current and future developments in this field.
基金funded under the Joint King’s College London/University of Malta agreement
文摘The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine—first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that（i） there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives;（ii） first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and（iii） maternal age at birth of the maxillary canine—first premolar transposition probands was significantly higher than that of the palatally displaced canine probands.The results suggest that maxillary canine—first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development.
基金Supported by the Slovenian Research Agency Research Programme,No.P1-0390,No.J3-7132,and No.Z3-2653.
文摘Psychiatric disorders,including suicide,are complex disorders that are affected by many different risk factors.It has been estimated that genetic factors contribute up to 50%to suicide risk.As the candidate gene approach has not identified a gene or set of genes that can be defined as biomarkers for suicidal behaviour,much is expected from cutting edge technological approaches that can interrogate several hundred,or even millions,of biomarkers at a time.These include the‘-omic’approaches,such as genomics,transcriptomics,epigenomics,proteomics and metabolomics.Indeed,these have revealed new candidate biomarkers associated with suicidal behaviour.The most interesting of these have been implicated in inflammation and immune responses,which have been revealed through different study approaches,from genome-wide single nucleotide studies and the micro-RNA transcriptome,to the proteome and metabolome.However,the massive amounts of data that are generated by the‘-omic’technologies demand the use of powerful computational analysis,and also specifically trained personnel.In this regard,machine learning approaches are beginning to pave the way towards personalized psychiatry.
基金supported by the fund from the National High Technology Research and Development Program of China to Z.Sun (No.2012AA02A202)
文摘Intensively developed in the last few years, single-cell sequencing technologies now present numerous advantages over traditional sequencing methods for solving the problems of biological heterogeneity and low quantities of available biological materials. The application of single-cell sequencing technologies has profoundly changed our understanding of a series of biological phenomena, including gene transcription, embryo development, and carcinogenesis. However, before single-cell sequencing technologies can be used extensively, researchers face the serious challenge of overcoming inherent issues of high amplification bias, low accuracy and repro- ducibility. Here, we simply summarize the techniques used for single-cell isolation, and review the current technologies used in single-cell genomic, transcriptomic, and epigenomic sequencing, We discuss the merits, defects, and scope of application of single-cell sequencing technologies and then speculate on the direction of future developments.
