Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.,Nature Cell Biology

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Single-cell chromatin accessibility maps reveal regulatory programs driving early mouse organogenesis.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2020-03-30 , DOI: 10.1038/s41556-020-0489-9
Blanca Pijuan-Sala _{1,

2} , Nicola K Wilson _{1,

2} , Jun Xia ₃ , Xiaomeng Hou ₄ , Rebecca L Hannah _{1,

2} , Sarah Kinston _{1,

2} , Fernando J Calero-Nieto _{1,

2} , Olivier Poirion ₄ , Sebastian Preissl ₄ , Feng Liu ₃ , Berthold Göttgens _{1,

2}

Affiliation

During mouse embryonic development, pluripotent cells rapidly divide and diversify, yet the regulatory programs that define the cell repertoire for each organ remain ill-defined. To delineate comprehensive chromatin landscapes during early organogenesis, we mapped chromatin accessibility in 19,453 single nuclei from mouse embryos at 8.25 days post-fertilization. Identification of cell-type-specific regions of open chromatin pinpointed two TAL1-bound endothelial enhancers, which we validated using transgenic mouse assays. Integrated gene expression and transcription factor motif enrichment analyses highlighted cell-type-specific transcriptional regulators. Subsequent in vivo experiments in zebrafish revealed a role for the ETS factor FEV in endothelial identity downstream of ETV2 (Etsrp in zebrafish). Concerted in vivo validation experiments in mouse and zebrafish thus illustrate how single-cell open chromatin maps, representative of a mammalian embryo, provide access to the regulatory blueprint for mammalian organogenesis.

中文翻译：

单细胞染色质可及性图揭示了驱动早期小鼠器官发生的调控程序。

在小鼠胚胎发育过程中，多能细胞迅速分裂和多样化，但定义每个器官的细胞库的调控程序仍然不明确。为了描绘早期器官发生过程中的全面染色质景观，我们在受精后 8.25 天绘制了小鼠胚胎 19,453 个单核的染色质可及性。开放染色质的细胞类型特异性区域的鉴定精确定位了两个 TAL1 结合的内皮增强子，我们使用转基因小鼠测定对其进行了验证。整合的基因表达和转录因子基序富集分析突出了细胞类型特异性转录调节因子。随后的斑马鱼体内实验揭示了 ETS 因子 FEV 在 ETV2（斑马鱼中的 Etsrp）下游内皮特性中的作用。因此，在小鼠和斑马鱼中进行的协调一致的体内验证实验说明了代表哺乳动物胚胎的单细胞开放染色质图谱如何为哺乳动物器官发生提供调控蓝图。

更新日期：2020-04-24

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