清华大学医学院蓝勋团队近期取得重要工作进展，他们研究绘制了小鼠器官发生中染色质可及性的单细胞图谱。相关研究成果2024年7月8日在线发表于《自然—细胞生物学》杂志上。

据介绍，器官发生是一个高度复杂和精确调控的过程。

研究人员通过SPATAC-seq分析了来自13个小鼠胚胎超过35万个细胞的染色质可及性。这些细胞处于从胚胎发生E10.5天到E13.5天的四个发育阶段。由此得到的图谱揭示了830873个候选顺式调控元件在43种主要细胞类型中的状态。通过将染色质可及性图谱与先前的转录组数据集相结合，研究人员表征了与细胞命运承诺相关的顺式调控序列和转录因子，如胃肠道发育中的Nr5a2，这在斑马鱼体内实验中得到了初步支持。

最后，研究人员将该图谱与之前来自13个成年小鼠组织的单细胞染色质可及性数据集相结合，以描述不同细胞类型内和不同细胞类型之间的发育阶段特异性基因调控程序，并确定整个谱系发育过程中的潜在分子转换。

总之，这一综合数据集为探索器官发生中的转录调控提供了基础。

附：英文原文

Title: A single-cell atlas of chromatin accessibility in mouse organogenesis

Author: Sun, Keyong, Liu, Xin, Lan, Xun

Issue&Volume: 2024-07-08

Abstract: Organogenesis is a highly complex and precisely regulated process. Here we profiled the chromatin accessibility in >350,000 cells derived from 13 mouse embryos at four developmental stages from embryonic day (E) 10.5 to E13.5 by SPATAC-seq in a single experiment. The resulting atlas revealed the status of 830,873 candidate cis-regulatory elements in 43 major cell types. By integrating the chromatin accessibility atlas with the previous transcriptomic dataset, we characterized cis-regulatory sequences and transcription factors associated with cell fate commitment, such as Nr5a2 in the development of gastrointestinal tract, which was preliminarily supported by the in vivo experiment in zebrafish. Finally, we integrated this atlas with the previous single-cell chromatin accessibility dataset from 13 adult mouse tissues to delineate the developmental stage-specific gene regulatory programmes within and across different cell types and identify potential molecular switches throughout lineage development. This comprehensive dataset provides a foundation for exploring transcriptional regulation in organogenesis.

DOI: 10.1038/s41556-024-01435-6

Source: https://www.nature.com/articles/s41556-024-01435-6