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多基因组分析揭示了原发性和有机基因衍生的人类肝细胞之间的独特基因调节机制

Haoyu Wu¹, Annie S P Yang², Suzan Stelloo^1,3

¹Department of Molecular Biology, Faculty of Science, Radboud Institute for Molecular Life Science, Radboud University, Nijmegen 6525GA, The Netherlands.

Disease models & mechanisms

|January 29, 2025

概括

研究人员确定了调节肝细胞成熟度的关键转录因子. 在有机体衍生的肝细胞中减少ELF3改善了肝脏关键标记物的表达,促进了肝脏模型的开发.

科学领域:

肝病学和再生医学肝病学和再生医学
基因组学和分子生物学

背景情况:

肝脏器官培养是一种有价值的体外模型,用于研究肝脏发育和疾病.
来自有机体的肝细胞样细胞通常与原发性人类肝细胞 (PHHs) 相比表现不成熟.

研究的目的:

与PHHs相比,阐明负责有机基因衍生肝细胞不成熟的基因调节机制.
识别转录因子,使成熟的肝细胞与不成熟的肝细胞有区别.

主要方法:

综合性单细胞转录组和染色质可访问性分析.
对PHHs和肝脏内胆固醇细胞有机体 (ICO) 衍生肝细胞的转录因子活性进行比较分析.
功能分析涉及ELF3耗尽.

主要成果:

激活蛋白1 (AP-1) 因子与成熟的人类肝细胞中的HNF4A等肝细胞特异性因子共同占据调节区域.
在PHHs和ICO衍生的肝细胞中,不同的转录因子集是活跃的.
在ICO衍生的肝细胞中,ELF3具有独特的表达,并且与肝脏标记物表达有负相关性;其枯竭增强了肝脏标记物表达.

结论:

综合性分析揭示了对转录性调节网络的洞察力,使初级肝细胞和有机体模型区分开来.
研究结果为开发更成熟,更准确的肝脏器官模型的研究和药物测试提供了信息.

关键词:

ELF3 ELF3 在线播放基因监管网络基因监管网络肝脏内胆固醇细胞有机体.主要的人类肝细胞这就是 scRNA-seqq.

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