VGLL1与TEAD4合作,控制人类托菲克托德尔玛谱系规范
Yueli Yang1, Wenqi Jia2,3,4, Zhiwei Luo2,3
1State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China.
Nature communications
|January 17, 2024
概括
遗体样家族成员1 (VGLL1) 对于人体皮的发育和胎盘的早期形成至关重要. 这种蛋白调节人类干细胞中的细胞命运和自我更新,为灵长类动物的胚胎生成提供了洞察力.
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
- 生殖生物学 生殖生物学
背景情况:
- 由于道德和实际的局限性,人们对人体托菲克托德和胎盘特异机制的了解很少.
- 人类多能干细胞 (PSC) 为研究早期胎盘发育提供了一个有前途的体外模型.
- 之前的研究表明,PSCs可以分化为肌肉外皮样细胞 (TELCs) 和热囊细胞干细胞 (TSCs).
研究的目的:
- 调查VGLL1 (形状家族成员1) 在人体皮和早期胎盘特异化中的作用.
- 阐明VGLL1调节人类TELC和TSC细胞命运和自我更新的分子机制.
- 为了比较灵长类早期胚胎发生与其他哺乳动物物种.
主要方法:
- 使用人类多能干细胞 (PSCs),分化成类似肌体细胞 (TELCs) 和肌体细胞干细胞 (TSCs).
- 在这些体外模型中研究了VGLL1的表达和功能.
- 分析了VGLL1与TEAD4,GATA3和TFAP2C等转录因子的相互作用.
- 检查了VGLL1在调节色素可访问性和素乙化在基因位置的作用.
主要成果:
- 在人类和非人类灵长类动物的肌体特异化过程中,VGLL1的表达很高,但在小鼠中没有.
- VGLL1是细胞命运决定和自我更新的关键调节者,在人类TELC和来自原始PSC的TSC中产生.
- VGLL1与TEAD4一起作用,通过基因素乙化控制染色质的可访问性,与GATA3和TFAP2C合作.
结论:
- VGLL1在人体皮的特异化和早期胎盘形成中起着至关重要的作用.
- 这些发现突显了灵长类动物和动物早期胚胎生成之间的关键差异.
- 这项研究为了解人类胎盘发育和相关疾病提供了一个有价值的体外模型.
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