异形细胞细胞系的发展与染色质景观的活跃重塑有关
Kaela M Varberg1,2, Esteban M Dominguez3,4, Boryana Koseva5
1Institute for Reproductive and Developmental Sciences, University of Kansas Medical Center, Kansas City, Kansas, 66160, USA. kvarberg@kumc.edu.
Nature communications
|August 10, 2023
概括
这项研究揭示了关键的基因调节者控制人类外性热囊细胞的发展,这对成功怀孕和胎盘形成至关重要. 了解这些调节网络为怀孕并发症提供了见解.
科学领域:
- 生殖生物学 生殖生物学
- 发展生物学 发展生物学
- 基因组学和表观基因组学
背景情况:
- 突发性多细胞细胞系对于人类的胎盘和怀孕成功至关重要.
- 有限的知识存在关于管理超性热细胞发育的转录调节.
- 了解这些调节机制对于解决妊娠并发症至关重要.
研究的目的:
- 为了绘制转录基因组,表观基因组和染色质相互作用在人体热原体干细胞分化到异常热原体细胞.
- 识别关键的转录因子和调控机制,驱动异常多细胞细胞的发展.
- 阐明特定转录因子在 trofhoblast 细胞系发展中的功能作用.
主要方法:
- 综合分析染色质可访问性,长距离染色质相互作用和转录基因数据.
- 转录因子结合动机丰富分析.
- 确定转录因子 (TFAP2C,SNAI1,EPAS1) 的功能阐明.
主要成果:
- 通过集成的多omics数据,成功地识别了关键的转录因子和监管机制,以促进外性热囊细胞的发展.
- 阐明TFAP2C,SNAI1和EPAS1在调节外性热原体细胞发育中的功能作用.
- EPAS1被确定为ASCL2和SNAI1的上游调节者,与妊娠损失和出生体重有关.
结论:
- 已经揭示了一个动态的调节网络,控制人类异常热囊细胞的特异性.
- 这项研究为了解热细胞细胞系的发展和人类胎盘形成提供了基础框架.
- 这些发现凸显了EPAS1及其下游目标对妊娠结果的重要性.
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