2025年7月8日,浙江大学医学院/良渚实验室郭国骥教授团队在《细胞》(Cell)上发表了题为“Modeling the vertebrate regulatory sequence landscape by UUATAC-seq and deep learning”的研究论文(DOI:10.1016/j.cell.2025.06.020)。该...2025年7月8日,浙江大学医学院/良渚实验室郭国骥教授团队在《细胞》(Cell)上发表了题为“Modeling the vertebrate regulatory sequence landscape by UUATAC-seq and deep learning”的研究论文(DOI:10.1016/j.cell.2025.06.020)。该研究建立了超高通量、超灵敏的单核ATAC测序技术(UUATAC-seq)。展开更多
Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economic...Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economically and ecologically important species in China.In the present study,RNA sequencing(RNA-seq)and assay for transposase-accessible chromatin using sequencing(ATAC-seq)were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents.Analysis identified 9483 differentially expressed genes(DEGs)and 7215 genes with significantly differential chromatin accessibility(DCAGs)were obtained,with an overlap of 2600 genes between them.Notably,a significant proportion of these genes were enriched in pathways related to glycogen metabolism,including“Glycogen metabolic process”and“Starch and sucrose metabolism”.In addition,genome-wide association study(GWAS)identified 526 single nucleotide polymorphism(SNP)loci associated with glycogen content.These loci corresponded to 241 genes,63 of which were categorized as both DEGs and DCAGs.This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C.ariakensis.展开更多
Single-cell chromatin accessibility analysis enables high-resolution dissection of regulatory elements and gene regulatory mechanisms.However,standardized and comprehensive analysis workflows remain limited.In this st...Single-cell chromatin accessibility analysis enables high-resolution dissection of regulatory elements and gene regulatory mechanisms.However,standardized and comprehensive analysis workflows remain limited.In this study,we present a streamlined pipeline for analyzing single-cell chromatin accessibility data.The workflow begins with data preprocessing using single-cell assay for transposase-accessible chromatin(scATAC)-pro or Cell Ranger ATAC,followed by peak calling with MACS2 and differential accessibility analysis to detect open chromatin regions and perform differential accessibility analysis to highlight regulatory differences among cell populations.Transcription factor activity is then inferred using chromVAR,incorporating motif enrichment and footprinting analysis.Finally,SCENIC+is applied to reconstruct transcriptional regulatory networks,enabling in-depth exploration of epigenetic mechanisms at the single-cell level.This integrative approach offers a robust framework for decoding the regulatory landscape and understanding cellular heterogeneity in complex biological systems.展开更多
Musk secreted by male forest musk deer(Moschus berezovskii)musk glands is an invaluable component of medicine and perfume.Musk secretion depends on musk gland maturation;however,the mechanism of its development remain...Musk secreted by male forest musk deer(Moschus berezovskii)musk glands is an invaluable component of medicine and perfume.Musk secretion depends on musk gland maturation;however,the mechanism of its development remains elusive.Herein,using single cell multiome ATAC+gene expression coupled with several bioinformatic analyses,a dynamic transcriptional cell atlas of musk gland development was revealed,and key genes and transcription factors affecting its development were determined.Twelve cell types,including two different types of acinar cells(Clusters 0 and 10)were identified.Single-nucleus RNA and single-nucleus ATAC sequencing analyses revealed that seven core target genes associated with musk secretion(Hsd17b2,Acacb,Lss,Vapa,Aldh16a1,Aldh7a1,and Sqle)were regulated by 12 core transcription factors(FOXO1,CUX2,RORA,RUNX1,KLF6,MGA,NFIC,FOXO3,ETV5,NR3C1,HSF4,and MITF)during the development of Cluster 0 acinar cells.Kyoto Encyclopedia of Genes and Genomes enrichment showed significant changes in the pathways associated with musk secretion during acinar cell development.Gene set variation analysis also revealed that certain pathways associated with musk secretion were enriched in 6-year-old acinar cells.A gene co-expression network was constructed during acinar cell development to provide a precise understanding of the connections between transcription factors,genes,and pathways.Finally,intercellular communication analysis showed that intercellular communication is involved in musk gland development.This study provides crucial insights into the changes and key factors underlying musk gland development,which serve as valuable resources for studying musk secretion mechanisms and promoting the protection of this endangered species.展开更多
Molybdenum cofactor(Moco)biosynthesis is linked to c-Jun N-terminal kinase(JNK)signaling in Drosophila through MoaE,a molybdopterin(MPT)synthase subunit that is also acomponent of theAdaTwoAcontaining(ATAC)acetyltrans...Molybdenum cofactor(Moco)biosynthesis is linked to c-Jun N-terminal kinase(JNK)signaling in Drosophila through MoaE,a molybdopterin(MPT)synthase subunit that is also acomponent of theAdaTwoAcontaining(ATAC)acetyltransferasecomplex.Here,weshow thathumanMPTsynthase and ATAC inhibited PKR,a double-stranded RNA-dependent protein kinase,to facilitate translation initiation of iron-responsive mRNA.MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2a(eIF2a).The suppression of eIF2a phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B,which recycles eIF2-GDP to eIF2-GTP,resulting in the promotion of translation initiation.Indeed,translation of the iron storage protein,ferritin,was reduced in the absence of MPT synthase or ATAC subunits.Thus,MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation.展开更多
Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA...Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.展开更多
文摘2025年7月8日,浙江大学医学院/良渚实验室郭国骥教授团队在《细胞》(Cell)上发表了题为“Modeling the vertebrate regulatory sequence landscape by UUATAC-seq and deep learning”的研究论文(DOI:10.1016/j.cell.2025.06.020)。该研究建立了超高通量、超灵敏的单核ATAC测序技术(UUATAC-seq)。
基金supported by the National Key R&D Program of China(2022YFD2400105,2018YFD0900104)Central Publicinterest Scientific Institution Basal Research Fund,CAFS(2021XT0102,2023TD30)+2 种基金Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(2021QNLM050103)Key Research and Development Project of Shandong Province(2021LZGC028)National Marine Genetic Resource Center。
文摘Glycogen serves as the principal energy reserve for metabolic processes in aquatic shellfish and substantially contributes to the flavor and quality of oysters.The Jinjiang oyster(Crassostrea ariakensis)is an economically and ecologically important species in China.In the present study,RNA sequencing(RNA-seq)and assay for transposase-accessible chromatin using sequencing(ATAC-seq)were performed to investigate gene expression and chromatin accessibility variations in oysters with different glycogen contents.Analysis identified 9483 differentially expressed genes(DEGs)and 7215 genes with significantly differential chromatin accessibility(DCAGs)were obtained,with an overlap of 2600 genes between them.Notably,a significant proportion of these genes were enriched in pathways related to glycogen metabolism,including“Glycogen metabolic process”and“Starch and sucrose metabolism”.In addition,genome-wide association study(GWAS)identified 526 single nucleotide polymorphism(SNP)loci associated with glycogen content.These loci corresponded to 241 genes,63 of which were categorized as both DEGs and DCAGs.This study enriches basic research data and provides insights into the molecular mechanisms underlying the regulation of glycogen metabolism in C.ariakensis.
基金supported by the Chinese Academy of Medical Sciences(CAMS)Innovation Funds for Medical Sciences(2024-I2M-3-001).
文摘Single-cell chromatin accessibility analysis enables high-resolution dissection of regulatory elements and gene regulatory mechanisms.However,standardized and comprehensive analysis workflows remain limited.In this study,we present a streamlined pipeline for analyzing single-cell chromatin accessibility data.The workflow begins with data preprocessing using single-cell assay for transposase-accessible chromatin(scATAC)-pro or Cell Ranger ATAC,followed by peak calling with MACS2 and differential accessibility analysis to detect open chromatin regions and perform differential accessibility analysis to highlight regulatory differences among cell populations.Transcription factor activity is then inferred using chromVAR,incorporating motif enrichment and footprinting analysis.Finally,SCENIC+is applied to reconstruct transcriptional regulatory networks,enabling in-depth exploration of epigenetic mechanisms at the single-cell level.This integrative approach offers a robust framework for decoding the regulatory landscape and understanding cellular heterogeneity in complex biological systems.
基金supported by the Science and Technology Project of the State Forestry Administration(20180109000005)the Science and Technology Promotion Project of Shaanxi Forestry Bureau(20180611000001)+1 种基金the Science and Technology Project of the National Forestry and Grass Administration(20191202000009)the Shaanxi Academy of Forestry Sciences(SXL(2020-0207)).
文摘Musk secreted by male forest musk deer(Moschus berezovskii)musk glands is an invaluable component of medicine and perfume.Musk secretion depends on musk gland maturation;however,the mechanism of its development remains elusive.Herein,using single cell multiome ATAC+gene expression coupled with several bioinformatic analyses,a dynamic transcriptional cell atlas of musk gland development was revealed,and key genes and transcription factors affecting its development were determined.Twelve cell types,including two different types of acinar cells(Clusters 0 and 10)were identified.Single-nucleus RNA and single-nucleus ATAC sequencing analyses revealed that seven core target genes associated with musk secretion(Hsd17b2,Acacb,Lss,Vapa,Aldh16a1,Aldh7a1,and Sqle)were regulated by 12 core transcription factors(FOXO1,CUX2,RORA,RUNX1,KLF6,MGA,NFIC,FOXO3,ETV5,NR3C1,HSF4,and MITF)during the development of Cluster 0 acinar cells.Kyoto Encyclopedia of Genes and Genomes enrichment showed significant changes in the pathways associated with musk secretion during acinar cell development.Gene set variation analysis also revealed that certain pathways associated with musk secretion were enriched in 6-year-old acinar cells.A gene co-expression network was constructed during acinar cell development to provide a precise understanding of the connections between transcription factors,genes,and pathways.Finally,intercellular communication analysis showed that intercellular communication is involved in musk gland development.This study provides crucial insights into the changes and key factors underlying musk gland development,which serve as valuable resources for studying musk secretion mechanisms and promoting the protection of this endangered species.
基金supported by private funding fromthe Stowers Institute for Medical Research to the Workman laboratory.
文摘Molybdenum cofactor(Moco)biosynthesis is linked to c-Jun N-terminal kinase(JNK)signaling in Drosophila through MoaE,a molybdopterin(MPT)synthase subunit that is also acomponent of theAdaTwoAcontaining(ATAC)acetyltransferasecomplex.Here,weshow thathumanMPTsynthase and ATAC inhibited PKR,a double-stranded RNA-dependent protein kinase,to facilitate translation initiation of iron-responsive mRNA.MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2a(eIF2a).The suppression of eIF2a phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B,which recycles eIF2-GDP to eIF2-GTP,resulting in the promotion of translation initiation.Indeed,translation of the iron storage protein,ferritin,was reduced in the absence of MPT synthase or ATAC subunits.Thus,MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation.
基金supported by the National Natural Science Foundation of China(31770935,81873531,31970616)the Distinguished Professorship Program of Jiangsu Province to YF+2 种基金the Distinguished Professorship Program of Jiangsu Province to RMthe National Undergraduate Training Programs for Innovation(201710304030Z)the National Undergraduate Training Programs for Innovation(201810304026Z).
文摘Noncoding“junk DNA”,which constitutes 98%of our genome,is now generally considered to play a fundamental role in the precise regulation of coding genes to establish cell identity.One feature of functional“junk DNA”is its accessibility.In cancer cells,aberrant chromatin accessibility is recognized as one of the major hallmarks.Understanding such events requires high-throughput screening,such as Assay for Transposase-Accessible Chromatin using sequencing(ATAC-seq),which generates large-scale data that are puzzling for biologists.However,existing web tools only support cell line data and lack high-quality clinical phenotypes or matched transcriptomes.Here,we developed Shiny Pan-cancer Accessible Chromatin Explorer(SPACE)as an all-in-one web server encompassing 562,709 regulatory elements in 404 patients across 23 cancer types.
