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科学家利用时钟样染色质可及性位点追踪单细胞演化
作者:小柯机器人 发布时间:2024/5/11 16:39:15

北京优乐复生科技有限责任公司Yi Zhang团队利用时钟样染色质可及性位点追踪单细胞演化。相关论文于2024年5月9日在线发表在《自然—生物技术》杂志上。

研究人员表示,单细胞染色质可及性测序(scATAC-seq)可通过表型相似性重建发育轨迹。然而,推断确切的发育轨迹是一项挑战。以前的研究表明,在特定的基因组区域存在与年龄相关的DNA甲基化(DNAm)变化,这些区域被称为时钟样差异甲基化位点(ClockDML)。年龄相关的DNAm可能来自于ClockDML的染色质可及性变化,也可能是染色质可及性变化的结果。随着细胞有丝分裂的进行,时钟样基因座上染色质可及性的异质性会降低,从而提供了有丝分裂年龄的衡量标准。
 
研究人员开发了一种名为EpiTrace的方法,它能从scATAC-seq数据中计算已打开的时钟样位点的比例,从而确定细胞年龄,并在各种细胞系和动物物种中进行谱系追踪。它与已知的发育层次结构一致,与基于DNAm的时钟有很好的相关性,并与基于突变的谱系追踪、RNA速度和干性预测相辅相成。将EpiTrace应用于scATAC-seq数据可揭示具有临床相关意义的生物学观点,范围从造血、器官发育、肿瘤生物学和免疫到皮层皱褶。

附:英文原文

Title: Tracking single-cell evolution using clock-like chromatin accessibility loci

Author: Xiao, Yu, Jin, Wan, Ju, Lingao, Fu, Jie, Wang, Gang, Yu, Mengxue, Chen, Fangjin, Qian, Kaiyu, Wang, Xinghuan, Zhang, Yi

Issue&Volume: 2024-05-09

Abstract: Single-cell chromatin accessibility sequencing (scATAC-seq) reconstructs developmental trajectory by phenotypic similarity. However, inferring the exact developmental trajectory is challenging. Previous studies showed age-associated DNA methylation (DNAm) changes in specific genomic regions, termed clock-like differential methylation loci (ClockDML). Age-associated DNAm could either result from or result in chromatin accessibility changes at ClockDML. As cells undergo mitosis, the heterogeneity of chromatin accessibility on clock-like loci is reduced, providing a measure of mitotic age. In this study, we developed a method, called EpiTrace, that counts the fraction of opened clock-like loci from scATAC-seq data to determine cell age and perform lineage tracing in various cell lineages and animal species. It shows concordance with known developmental hierarchies, correlates well with DNAm-based clocks and is complementary with mutation-based lineage tracing, RNA velocity and stemness predictions. Applying EpiTrace to scATAC-seq data reveals biological insights with clinically relevant implications, ranging from hematopoiesis, organ development, tumor biology and immunity to cortical gyrification.

DOI: 10.1038/s41587-024-02241-z

Source: https://www.nature.com/articles/s41587-024-02241-z

期刊信息

Nature Biotechnology:《自然—生物技术》,创刊于1996年。隶属于施普林格·自然出版集团,最新IF:68.164
官方网址:https://www.nature.com/nbt/
投稿链接:https://mts-nbt.nature.com/cgi-bin/main.plex