布拉玛保护心脏中皮层分化的通道
Swetansu K Hota1,2,3, Kavitha S Rao4,5, Andrew P Blair4
1Gladstone Institutes, San Francisco, CA, USA. swetansu.hota@gladstone.ucsf.edu.
Nature
|January 27, 2022
概括
在发育过程中,Brm基因保护细胞的身份. Brm的损失导致胚胎干细胞从心脏转向神经命运,揭示了它在维持发育轨迹中的作用.
科学领域:
- 发育生物学
- 干细胞生物学
- 染色体重塑
背景情况:
- 在分化过程中,细胞命运的决定被道化稳定,但基本的机制仍然不太清楚.
- BRG1/BRM相关因子 (BAF) 染色体重塑复合体在调节基因可访问性和细胞身份方面发挥作用.
研究的目的:
- 研究brm基因在定向心脏发生过程中维持细胞身份的作用.
- 阐明 Brm 保护中皮细胞命运的分子机制.
主要方法:
- 使用的小鼠胚胎干细胞 (Brm-/-) 进行定向心脏生成.
- 使用轨迹推断来分析细胞命运过渡.
- 研究了染色体的可访问性,基因表达 (POU3F1,REST) 和蛋白质复合物的组成.
- 使用数学建模和体内小鼠胚胎研究.
主要成果:
- Brm-/-细胞主要采用神经前体命运,偏离半皮分配.
- 失去了Bm,心脏增强剂的可用性受损,神经因子POU3F1的表达增加.
- Brm删除转移了BRG1复合物的组成,并阻止了REST结合.
- 增加BMP4的水平挽救了Brm-/-细胞身份切换.
- 在体内,brm删除加剧了中皮缺陷的表型,影响了心脏发生.
结论:
- Brm作为中皮色素状态和细胞身份的关键保护.
- 发展道是一个可塑的过程, 而不是一个不可逆转的路径.
- 在体内,brm在保护心脏生成和胚胎层的忠实性方面发挥着重要作用.
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