HBO1确定了SMAD在多能性和介质皮的特征中的作用
Cong Zhang1,2,3, Yongli Shan1,2,3, Huaisong Lin1,2,3
1Key Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530,China; Guangzhou Medical University, Guangzhou 511436, China.
Nucleic acids research
|February 29, 2024
概括
在人类胚胎干细胞 (hESCs) 中,HBO1对于TGF-β信号传递至关重要,调节多能性和介质皮特异性. 缺少HBO1会损害这些过程,突出其作为细胞内在决定因素的作用.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 转化增长因子-β (TGF-β) 信号传递对于多能性和谱系特异性期间的细胞命运决定至关重要.
- 控制TGF-β家族信号传递的精确细胞内机制仍然不完全理解.
研究的目的:
- 为了研究HBO1的作用,一个MYST基因组酸转移酶 (HAT),作为一个细胞内在的因素,TGF-β信号在人类胚胎干细胞 (hESCs).
- 阐明HBO1影响多能性维护和谱系规范的分子机制.
主要方法:
- 使用了HBO1淘汰赛 (HBO1-/-) 人类胚胎干细胞 (hESC).
- 评估细胞对TGF-β信号的反应,包括维持多能性和分化潜力.
- 分析了使用BMP4触发的胃类动物和瘤的介质皮肤特征.
- 通过共免疫沉和染色体免疫沉 (ChIP) 试验,研究了HBO1和SMAD4之间的分子相互作用.
- 在分化过程中检查了基因素修饰 (H3K14ac,H3K4me3) 和基因表达模式.
主要成果:
- HBO1-/- hESCs表现出TGF-β信号受损,无法保持多能性,并经历自发的神经外皮分化.
- 在BMP4治疗的胃类动物和瘤中,HBO1缺乏完全废除了介质皮的特征.
- 在未分化的hESC中,HBO1与SMAD4相互作用,并与H3K14ac和H3K4me3标记的开放色素区域共结合.
- 在BMP4诱导的分化过程中,HBO1/SMAD4复合体保持了中皮基因表达,但在双SMAD抑制诱导的神经分化过程中,它从染色质中消失了.
结论:
- 在hESC中,HBO1充当TGF-β信号传递的细胞内在决定因素.
- HBO1对于维持多能性和指定中皮的命运都至关重要.
- HBO1的功能与它与SMAD4的相互作用以及它在调节关键发育基因中的染色质可访问性方面的作用有关.
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