单细胞染色质转座酶可及性的高通量测序(single-cell assay for transposase-accessible chromatin with high-throughput sequencing,scATAC-seq)是利用转座酶研究单细胞染色质开放性的高通量测序技术,对于研究全基因组的表观遗传调控...单细胞染色质转座酶可及性的高通量测序(single-cell assay for transposase-accessible chromatin with high-throughput sequencing,scATAC-seq)是利用转座酶研究单细胞染色质开放性的高通量测序技术,对于研究全基因组的表观遗传调控具有重要的意义。可从多个维度揭示有关染色质“组装”的重要信息,从而映射出细胞中的转录因子调控蛋白的结合区域和核小体定位等信息。目前,scATAC-seq技术已在生物和医学领域得到广泛应用,主要用于开放染色质图谱的绘制、细胞分化和发育、疾病致病机制以及肿瘤微环境的研究。本文阐述了scATAC-seq技术研究单细胞染色质开放区域的发展概况、数据分析和相关应用,期望对单细胞全基因组水平的染色质开放区域研究、顺式调控元件鉴定以及遗传调控网络的解析等提供借鉴,以期为今后更好的在生命科学研究中起到推动作用。展开更多
Dear Editor,The breakthrough in single-cell omics sequencing technologies has provided an unprecedented level of detail,allowing biologists to explore the patterns of gene activity,and the dynamics of cellular functio...Dear Editor,The breakthrough in single-cell omics sequencing technologies has provided an unprecedented level of detail,allowing biologists to explore the patterns of gene activity,and the dynamics of cellular function at the resolution of individual cells.At the forefront of this revolution is single-cell RNA sequencing(scRNA-seq),which measures gene expression of individual cells to characterize transcriptional heterogeneity.Additionally,other single-cell assays,such as single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq),shed light on cellular heterogeneity at the epigenetic level,enhancing our understanding of transcriptional regulation.However,while single-omics sequencing techniques provide valuable insights,they may not capture the intricate relationships between biomolecules in single cells due to their restriction to only one type of omics data.To bridge this gap,recent advancements have led to the development of several joint profiling methods(Cao et al.,2018;Chen et al.,2019;Luecken et al.,2021;Ma et al.,2020),which enable the simultaneous measurement of gene expression and chromatin accessibility,offering a holistic view of the gene regulatory landscape in individual cells.展开更多
The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT cells across tissues remains unc...The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT cells across tissues remains unclear.By combining transcriptional and chromatin analyses with a truly unbiased fashion,we constructed a single-cell transcriptome and chromatin accessibility landscape of mouseγδT cells in the lymph,spleen,and thymus.We also revealed the heterogeneity ofγδT1 andγδT17 cells across these tissues and inferred their potential regulatory mechanisms.In the thymus,we reconstructed the developmental trajectory and gained further insights into the signature genes from the mature stage,intermediate stage,and immature stage ofγδT cells on the basis of single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing data.Notably,a novel Gzma^(+)γδT cell subset was identified with immature properties and only localized to the thymus.Finally,NR1 D1,a circadian transcription factor(TF),was validated as a key and negative regulator ofγδT17 cell differentiation by performing a combined analysis of TF motif enrichment,regulon enrichment,and Nr1 d1 knockout mice.In summary,our data represent a comprehensive mapping on the transcriptome and chromatin accessibility dynamics of mouseγδT cells,providing a valuable resource and reference for future studies onγδT cells.展开更多
文摘单细胞染色质转座酶可及性的高通量测序(single-cell assay for transposase-accessible chromatin with high-throughput sequencing,scATAC-seq)是利用转座酶研究单细胞染色质开放性的高通量测序技术,对于研究全基因组的表观遗传调控具有重要的意义。可从多个维度揭示有关染色质“组装”的重要信息,从而映射出细胞中的转录因子调控蛋白的结合区域和核小体定位等信息。目前,scATAC-seq技术已在生物和医学领域得到广泛应用,主要用于开放染色质图谱的绘制、细胞分化和发育、疾病致病机制以及肿瘤微环境的研究。本文阐述了scATAC-seq技术研究单细胞染色质开放区域的发展概况、数据分析和相关应用,期望对单细胞全基因组水平的染色质开放区域研究、顺式调控元件鉴定以及遗传调控网络的解析等提供借鉴,以期为今后更好的在生命科学研究中起到推动作用。
基金supported by the National Natural Science Foundation of China (Grant Nos. 62203236, 62473212)the Young Elite Scientists Sponsorship Program by CAST (2023QNRC001)+1 种基金the Young Elite Scientists Sponsorship Program by BAST (BYESS2023383)the Emerging Interdisciplinary Platform for Medicine and Engineering in Sports (EIPMES)
文摘Dear Editor,The breakthrough in single-cell omics sequencing technologies has provided an unprecedented level of detail,allowing biologists to explore the patterns of gene activity,and the dynamics of cellular function at the resolution of individual cells.At the forefront of this revolution is single-cell RNA sequencing(scRNA-seq),which measures gene expression of individual cells to characterize transcriptional heterogeneity.Additionally,other single-cell assays,such as single-cell assay for transposase-accessible chromatin using sequencing(scATAC-seq),shed light on cellular heterogeneity at the epigenetic level,enhancing our understanding of transcriptional regulation.However,while single-omics sequencing techniques provide valuable insights,they may not capture the intricate relationships between biomolecules in single cells due to their restriction to only one type of omics data.To bridge this gap,recent advancements have led to the development of several joint profiling methods(Cao et al.,2018;Chen et al.,2019;Luecken et al.,2021;Ma et al.,2020),which enable the simultaneous measurement of gene expression and chromatin accessibility,offering a holistic view of the gene regulatory landscape in individual cells.
基金supported by the National Natural Science Foundation of China(31830021,32030036,32000615,and 32100695)the National Key Research and Development Program of China(2020YFA0803502)+2 种基金the 111 Project(B16021)China Postdoctoral Science Foundation(2020M683180,2019M663374,and 2020T130251)Guangdong Basic and Applied Basic Research Foundation(2020A1515111045 and 2020A1515111081)。
文摘The distinct characteristics ofγδT cells determine their vital roles in the formation of local immune responses and contribute to tissue homeostasis.However,the heterogeneity ofγδT cells across tissues remains unclear.By combining transcriptional and chromatin analyses with a truly unbiased fashion,we constructed a single-cell transcriptome and chromatin accessibility landscape of mouseγδT cells in the lymph,spleen,and thymus.We also revealed the heterogeneity ofγδT1 andγδT17 cells across these tissues and inferred their potential regulatory mechanisms.In the thymus,we reconstructed the developmental trajectory and gained further insights into the signature genes from the mature stage,intermediate stage,and immature stage ofγδT cells on the basis of single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing data.Notably,a novel Gzma^(+)γδT cell subset was identified with immature properties and only localized to the thymus.Finally,NR1 D1,a circadian transcription factor(TF),was validated as a key and negative regulator ofγδT17 cell differentiation by performing a combined analysis of TF motif enrichment,regulon enrichment,and Nr1 d1 knockout mice.In summary,our data represent a comprehensive mapping on the transcriptome and chromatin accessibility dynamics of mouseγδT cells,providing a valuable resource and reference for future studies onγδT cells.
