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单克隆性胃类动物的血统记录揭示了早期发育的遗传模式

Samuel G Regalado, Chengxiang Qiu, Sanjay Kottapalli

bioRxiv : the preprint server for biology

|June 6, 2025

概括

小鼠胚胎干细胞 (mESCs) 在形成胃类细胞时表现出显著的变异. 在mESCs中的可遗传细胞状态波动会影响它们的发育命运,影响胃类异质性.

科学领域:

发展生物学发展生物学
干细胞生物学干细胞生物学
基因组学就是基因组学.

背景情况:

哺乳动物干细胞自组织成复杂的结构用于体外发育模型.
在干细胞衍生模型中,即使在受控条件下,也存在显著的个人间异质性.

研究的目的:

调查胃类动物中异质性的起源,这是早期胚胎发育的模型.
确定小鼠胚胎干细胞 (mESCs) 的内在状态如何影响胃体形成和细胞类型组成.

主要方法:

开发了一个可扩展的协议,用于从单个mESCs生成单克隆性胃类.
利用单细胞转录概况来分析胃类异质性.
使用DNA打字机记录和重建细胞谱系关系.

主要成果:

单克隆性胃类动物在细胞类型组成和发育进展方面表现出广泛的异质性.
在胃类诱导之前,在创始mESC中观察到命运偏差和限制的证据.
重建了一个高分辨率的血统树,显示相关的创始细胞产生更相似的胃类动物.

结论:

内在mESC状态的遗传性波动对细胞分裂的发育异质性有显著的贡献.
"DNA打字机"是一个强大的工具,用于在干细胞模型中重建详细的细胞谱系树.
了解mESC异质性对于完善早期发育的体外模型至关重要.

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