在SOX4先驱因子活动活动启动的体内细胞重编程
Takeshi Katsuda1,2,3,4, Jonathan H Sussman1,2,3,5, Kenji Ito1,6
1Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature communications
|February 26, 2024
概括
SOX4通过首先沉默肝细胞基因,然后激活胆汁细胞基因来启动肝细胞代谢. 这项研究揭示了动物模型中细胞命运切换的分子机制.
科学领域:
- 细胞生物学 细胞生物学
- 发育生物学是发展生物学.
- 分子生物学分子生物学
背景情况:
- 组织损伤触发细胞命运切换通过转化成形.
- 沉默原始细胞命运并激活活体内的新命运的机制仍然不清楚.
- 细胞培养中的先驱转录因子通过改变染色质可访问性来调节重编程.
研究的目的:
- 调查SOX4在成人小鼠肝脏中启动肝胆代谢的作用.
- 了解SOX4介导的染色质在调节序列中的变化的时间动态.
- 阐明在生理细胞命运过渡期间基因网络重编程的层次结构.
主要方法:
- 使用谱系追踪成年老鼠肝脏模型.
- 评估SOX4对肝细胞和胆道细胞增强剂的直接结合和调节作用.
- 分析对SOX4表达的反应中的染色质可访问性变化.
主要成果:
- 在小鼠中,SOX4足以诱导肝胆代谢.
- SOX4最初通过与HNF4A相互作用,结合并抑制肝细胞调节序列.
- 随后,SOX4作为开放胆管调节序列的先驱因素.
结论:
- SOX4通过顺序沉默和激活特定的基因网络来协调细胞命运过渡.
- 这些发现提供了对体内甲质开始的机制的理解.
- 这项工作加深了对动物细胞命运可塑性的分子基础的洞察力.
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