开拓因素决定了干细胞可塑性和血统选择中的超强增强器动态
Rene C Adam1, Hanseul Yang1, Shira Rockowitz2
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology &Development, The Rockefeller University, New York, New York 10065, USA.
Nature
|March 25, 2015
概括
超级增强剂通过动态重塑染色体来控制成年干细胞的身份和可塑性. 这些调节元素对于血统承诺和适应不断变化的微环境至关重要,如毛囊干细胞所示.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 染色体的调节 染色体调节
背景情况:
- 成人干细胞通过自我更新和在特定的利基内对血统的承诺来维持组织静止.
- 在本地环境之外的干细胞表现出增加的命运灵活性.
- 超级增强剂是控制各种细胞类型基因表达的关键调控元素.
研究的目的:
- 调查超级增强剂在成年干细胞身份,血统承诺和可塑性中的作用.
- 在毛囊干细胞及其祖先中绘制染色体域和超强增强器动态图.
- 了解微环境线索如何通过超强增强器重塑影响干细胞命运.
主要方法:
- 在原生毛囊微环境中染色体域映射.
- 在谱系进展过程中分析超强增强剂和转录因子结合部位动态.
- 在体外和伤口修复模型研究干细胞可塑性.
- 识别和功能验证关键的监管器,如SOX9.
主要成果:
- 超级增强剂及其转录因子结合集群 (中心) 在谱系进展过程中重塑.
- 成人干细胞因微环境变化而动态重塑超级增强剂,无论是在体外还是在伤口修复过程中.
- SOX9作为毛囊干细胞超强增强剂的关键调节者,影响干细胞和分化.
- 超级增强器是对主调节器敏感的动态平台,定义了血统状态和可塑性.
结论:
- 超级增强剂对于保持成年干细胞身份,推动血统承诺和实现可塑性至关重要.
- 超强增强剂的动态重塑使干细胞能够适应不断变化的环境和状态之间的过渡.
- 针对超强增强剂调节,可能通过SOX9等因素,为控制干细胞行为提供了洞察力,用于再生目的.
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