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Isolation Method for Long-Term and Short-Term Hematopoietic Stem Cells
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表观遗传记忆是血造干细胞的细胞自主异质行为的基础
Vionnie W C Yu1, Rushdia Z Yusuf1, Toshihiko Oki1
1Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Cell
|November 19, 2016
概括
血造干细胞 (HSC) 表现出克隆特异性的功能,由表观遗传编程驱动. 这种细胞自主性凸显了HSC在维持组织平衡和修复方面的异质性.
科学领域:
- 干细胞生物学
- 血液形成
- 表观遗传学
背景情况:
- 干细胞对于组织平衡和修复至关重要.
- 在干细胞群体中越来越多地认识到功能异质性.
- 了解干细胞异质性是再生医学的关键.
研究的目的:
- 研究血造干细胞 (HSC) 功能异质性的程度和分子基础.
- 将功能属性与克隆级别的转录和表观遗传特征相关联.
主要方法:
- 在造血干细胞 (HSC) 中使用内源光标记.
- 在克隆水平上叠加功能,转录和表观遗传属性.
- 在恒常和压力条件下 (移植,炎症,基因毒性损伤) 分析了克隆行为.
主要成果:
- 随着时间的推移,确定了内源性HSC的克隆特异性功能属性.
- 在各种压力条件下表现出刻板和保存的克隆内行为.
- 将HSC功能与不同的转录,DNA甲基化和染色质可访问性模式联系起来.
- 观察到与表观遗传结构相关的HSC功能,但并不总是转录状态.
结论:
- 血液形成涉及具有表观遗传特征的异质HSC克隆.
- 表观遗传结构显著影响HSC功能和细胞自主性.
- 这些发现表明需要对干细胞可塑性和干细胞的概念进行细化.
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