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在肝损伤期间,HBO1作为肝细胞可塑性和重编程的表观遗传障碍
Wei-Chien Yuan1, Andrew S Earl2, Sai Ma3
1Stem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA; Department of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan; Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan.
肝细胞在肝损伤时可以转化为胆汁细胞,但表观遗传学尚不清楚. 我们发现,HBO1通过控制染色质来抑制这种重编程,这表明HBO1抑制可以帮助肝脏再生.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞重编程 细胞重编程
- 肝脏生物学 肝脏生物学
背景情况:
- 肝细胞可以在肝损伤后转化为胆道上皮细胞 (BEC).
- 控制这种肝细胞到BEC重编程的表观遗传机制尚不清楚.
研究的目的:
- 阐明肝细胞重编程成BECs的表观遗传动力学和关键调节剂.
- 为了确定那些作为细胞可塑性障碍的因素.
主要方法:
- 单细胞ATAC-seq用于分析重编程期间的染色质可访问性.
- 在体内进行CRISPR查以识别关键基因.
- 测试用于评估基因素修饰和蛋白质相互作用.
主要成果:
- 在重编程肝细胞中,YAP/TEAD通路的激活驱动着染色质重塑.
- 基因组酸转移酶HBO1作为一个屏障,被YAP招募来抑制目标基因转录.
- HBO1促进H3K14ac,并与ZMYND8相互作用以抑制重编程.
- 失去HBO1会加速染色质的变化,并增强肝细胞到BEC的过渡.
结论:
- HBO1 作为YAP介导的肝细胞重编程的表观遗传车.
- 向HBO1可能会增强肝细胞的可塑性,促进肝脏的再生.
- 了解这些表观遗传控制对于开发肝病治疗方法至关重要.
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