清華大學(xué)醫(yī)學(xué)院藍勛團隊近期取得重要工作進展，他們研究繪制了小鼠器官發(fā)生中染色質(zhì)可及性的單細胞圖譜。相關(guān)研究成果2024年7月8日在線發(fā)表于《自然—細胞生物學(xué)》雜志上。
據(jù)介紹，器官發(fā)生是一個高度復(fù)雜和精確調(diào)控的過程。
研究人員通過SPATAC-seq分析了來自13個小鼠胚胎超過35萬個細胞的染色質(zhì)可及性。這些細胞處于從胚胎發(fā)生E10.5天到E13.5天的四個發(fā)育階段。由此得到的圖譜揭示了830873個候選順式調(diào)控元件在43種主要細胞類型中的狀態(tài)。通過將染色質(zhì)可及性圖譜與先前的轉(zhuǎn)錄組數(shù)據(jù)集相結(jié)合，研究人員表征了與細胞命運承諾相關(guān)的順式調(diào)控序列和轉(zhuǎn)錄因子，如胃腸道發(fā)育中的Nr5a2，這在斑馬魚體內(nèi)實驗中得到了初步支持。
最后，研究人員將該圖譜與之前來自13個成年小鼠組織的單細胞染色質(zhì)可及性數(shù)據(jù)集相結(jié)合，以描述不同細胞類型內(nèi)和不同細胞類型之間的發(fā)育階段特異性基因調(diào)控程序，并確定整個譜系發(fā)育過程中的潛在分子轉(zhuǎn)換。
總之，這一綜合數(shù)據(jù)集為探索器官發(fā)生中的轉(zhuǎn)錄調(diào)控提供了基礎(chǔ)。
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
期刊信息
Nature Cell Biology：《自然—細胞生物學(xué)》，創(chuàng)刊于1999年。隸屬于施普林格·自然出版集團，最新IF：28.213
官方網(wǎng)址：https://www.nature.com/ncb/
投稿鏈接：https://mts-ncb.nature.com/cgi-bin/main.plex
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