单细胞命运和功能的有限可塑性与祖先水平的表观遗传脚本相关
Catherine Rhee1,2,3, Elizabeth W Scadden1,2,3, Lai Ping Wong4,5
1Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA.
Blood
|June 2, 2023
概括
单细胞亚型具有独特的,固有的功能,由祖先表观基因组决定,而不是环境线索. 这些功能上受限制的髓状细胞子集具有有限的可塑性,影响了体内传染病的控制.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 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.
背景情况:
- 髓状细胞的异质性是公认的,但这种多样性的驱动因素 (内在与环境) 仍在争论中.
- 了解单细胞子集特征对于它们在免疫和疾病中的作用至关重要.
研究的目的:
- 调查髓状细胞异质性的内在性与环境驱动性.
- 定义单细胞子集的功能特征和可塑性.
主要方法:
- 利用一种可诱导/可逆系统暂停骨髓分化,使得克隆特异性的功能分析.
- 基于分子特征,在各种条件下的可塑性 (静止,辐射,感染) 和体内感染病原体控制的单细胞子集的特征.
主要成果:
- 识别了具有明显分子特征的单细胞子集,独立于经典/非经典分类.
- 证明子集特征是固有的,在表观遗传上受到祖先染色质可访问性的约束,并表现出有限的可塑性.
- 通过不同的初级单细胞子集展示了在体内对传染病原体的差异性控制.
结论:
- 单细胞包括由原生表观基因组定义的功能限制的亚型.
- 这些亚型具有有限的可塑性,它们的命运在发育早期就被确定了.
- 生理挑战差异地选择这些亚型,影响免疫反应.
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