先进的SOX9因子与表观遗传因子竞争,改变干细胞命运
Yihao Yang1, Nicholas Gomez1,2, Nicole Infarinato1,3
1Howard Hughes Medical Institute, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY, USA.
SOX9主调节器通过打开新的增强剂和沉默旧的,将表皮干细胞重定向到毛囊命运. 成人干细胞中异常的SOX9激活可能导致癌症.
科学领域:
- 发育生物学是发展生物学.
- 干细胞生物学 干细胞生物学
- 癌症生物学 癌症生物学
背景情况:
- 细胞命运决定涉及同时激活和沉默血统,这对于成年干细胞至关重要,但在癌症中经常失调.
- 像SOX9这样的先驱因子将闭合色素结合以启动血统切换,但它们的精确机制仍然不清楚.
研究的目的:
- 为了研究SOX9,一个主调节器,如何驱动皮肤上干细胞 (EpdSCs) 到毛囊干细胞的命运切换.
- 阐明成人EpdSCs中SOX9介导的谱系可塑性背后的表观遗传学和转录力学.
主要方法:
- 工程小鼠在成年EpdSCs中重新表达SOX9.
- 利用表观遗传学,蛋白质学和功能分析来研究染色体和转录变化.
- 研究EpdSC利基微环境在调节这些动态中的作用.
主要成果:
- 在EpdSCs中,SOX9 de novo结合和毛囊增强剂的开放.
- 从表皮增强剂中招募辅助因子,导致它们沉默.
- 确定持续的SOX9诱导的瘤转录调节器的激活.
结论:
- SOX9通过动态重塑染色体可访问性和转录因子占用率来调节干细胞命运切换.
- 成人干细胞中SOX9的失调可以启动致癌途径,导致癌症的发展.
- EpdSC 利基微环境影响SOX9驱动的命运转换的时间动态.
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