SOX17是人类原始生殖细胞命运的关键特征
Naoko Irie1, Leehee Weinberger2, Walfred W C Tang1
1Wellcome Trust Cancer Research UK Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 1QN, UK; Department of Physiology, Development and Neuroscience, Downing Street, University of Cambridge, Cambridge CB2 3EG, UK; Wellcome Trust-Medical Research Council Stem Cell Institute, Tennis Court Road, University of Cambridge, Cambridge CB2 3EG, UK.
Cell
|December 29, 2014
概括
研究人员从多能干细胞创建了人类原始生殖细胞样细胞 (hPGCLCs). SOX17和BLIMP1是关键的调节剂,揭示了与小鼠生殖细胞发育的差异.
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:
- 原始生殖细胞 (PGCs) 启动全能状态,这对繁殖至关重要.
- 由于缺乏实验模型,控制人类PGC (hPGC) 规范的精确机制尚未完全理解.
研究的目的:
- 为研究人类PGC规范建立一个可操作的实验模型.
- 确定参与hPGC规范的关键分子调节剂.
- 将人类的PGC规范机制与其他物种 (如小鼠) 的规范机制进行比较.
主要方法:
- 人类PGC类细胞 (hPGCLCs) 从生殖系竞争力的多能干细胞的特征.
- 描述hPGCLCs,将它们与胚胎hPGCs和生殖细胞瘤进行比较.
- 分析关键的转录因子,包括SOX17和BLIMP1,使用细胞表面标记物CD38作为参考.
主要成果:
- 成功生成了hPGCLCs,表现出与胚胎hPGCs和生殖线精子瘤一致的特征.
- 确定SOX17是促进hPGCLC命运的关键调节者.
- 证明BLIMP1的功能在hPGCLC规范过程中抑制内皮和体内基因表达,与小鼠PGC发育相比,突出了与物种特定的差异.
结论:
- 这项研究为研究人类生殖线发育和PGC规范提供了基础模型.
- SOX17和BLIMP1在人类与小鼠的PGC规范中发挥着关键的,可能不同的作用.
- 这项工作为未来研究hPGCLCs和hPGCs的表观遗传重编程以实现全能性的研究奠定了基础.
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