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科学家建立单细胞染色质可及性和基因表达的多模式分析方法
作者:小柯机器人 发布时间:2022/9/18 16:41:21

南方科技大学Xi Chen和Wenfei Jin课题组合作的研究发现,ISSAAC-seq可对单个细胞的染色质可及性和基因表达进行灵敏灵活的多模式分析。相关论文于2022年9月15日发表在《自然-方法学》杂志上。

研究人员研发了在转座酶可及染色质测序(ISSAAC-seq)分析后的原位测序异源RNA-DNA-hybrid,这是一种高度灵敏和灵活的单细胞多组学方法,用于检测单细胞核中染色质可及性和基因表达。研究表明ISSAAC-seq高度灵敏并且可以提供比现有方法高多个数量级的高质量数据。

分析小鼠大脑皮层的10,000多个细胞核关节图谱,研究发现了主要和罕见的细胞类型和细胞类型特异性调控元件,并且在基因表达确定的细胞类型中确定了染色质水平异质性。最后,研究揭示了在少突胶质细胞成熟过程中基因表达和染色质可及性的不同动态和关系。

据介绍,单个细胞的染色质可及性和基因表达联合分析,提供了有关动态过程中组织细胞类型和细胞状态的关键信息。

附:英文原文

Title: ISSAAC-seq enables sensitive and flexible multimodal profiling of chromatin accessibility and gene expression in single cells

Author: Xu, Wei, Yang, Weilong, Zhang, Yunlong, Chen, Yawen, Hong, Ni, Zhang, Qian, Wang, Xuefei, Hu, Yukun, Song, Kun, Jin, Wenfei, Chen, Xi

Issue&Volume: 2022-09-15

Abstract: Joint profiling of chromatin accessibility and gene expression from the same single cell provides critical information about cell types in a tissue and cell states during a dynamic process. Here, we develop in situ sequencing hetero RNA–DNA-hybrid after assay for transposase-accessible chromatin-sequencing (ISSAAC-seq), a highly sensitive and flexible single-cell multi-omics method to interrogate chromatin accessibility and gene expression from the same single nucleus. We demonstrated that ISSAAC-seq is sensitive and provides high quality data with orders of magnitude more features than existing methods. Using the joint profiles from over 10,000 nuclei from the mouse cerebral cortex, we uncovered major and rare cell types and cell-type specific regulatory elements and identified heterogeneity at the chromatin level within established cell types defined by gene expression. Finally, we revealed distinct dynamics and relationships of gene expression and chromatin accessibility during an oligodendrocyte maturation trajectory.

DOI: 10.1038/s41592-022-01601-4

Source: https://www.nature.com/articles/s41592-022-01601-4

期刊信息

Nature Methods:《自然—方法学》,创刊于2004年。隶属于施普林格·自然出版集团,最新IF:28.467
官方网址:https://www.nature.com/nmeth/
投稿链接:https://mts-nmeth.nature.com/cgi-bin/main.plex