自新的人类原始多能干细胞在3D培养中脱差,并自发地形成布拉斯泰体
Mingyue Guo1,2,3,4, Jinyi Wu5,6,7, Chuanxin Chen5,6,7,8
1Guangzhou Medical University, Guangzhou, Guangdong, China. guo_mingyue@gzlab.ac.cn.
Nature communications
|January 22, 2024
概括
人类原始多能干细胞 (hnPSCs) 在3D培养中自发形成布拉斯体. 这一由GSK3抑制驱动的过程涉及到将胚胎样中间体分化为建立胚胎细胞细胞命运的胚胎样中间体.
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
- 人类胚胎发生
背景情况:
- 人类原始多能干细胞 (hnPSCs) 可以通过形成Blastoids来模拟早期人类发育.
- 驱动hnPSC自发发芽细胞形成的机制尚不清楚.
研究的目的:
- 在3D培养中阐明从hNPSC中自发发形成的状体的机制.
- 描述参与这个过程的发育潜力和细胞中间体.
主要方法:
- 自行更新的 hnPSCs 的 3D 悬浮培养.
- 对自发发芽细胞的转录组分析.
- 对糖原合成酶激酶-3 (GSK3) 信号抑制的研究.
主要成果:
- 自行更新的hNPSC在3D培养中自发生成了体,模仿人类的体.
- 在5iLAF介质中的GSK3抑制剂IM-12上调了氧化酸化基因的调节,从而使自发的布拉斯泰菌形成.
- hnPSCs被分化为SOX2/OCT4和GATA6共同表达的中间体,确定了热囊细胞的命运,并导致了状体的形成.
结论:
- 自发的布拉斯形形成是由3D培养条件引发的,这些条件诱导了hNPSC脱差.
- 不分化的中间体有能力分离胚胎细胞系,为早期人类发育提供了一种新型模型.
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