单细胞血统追踪揭示了TCF15在血液形成中的作用
Alejo E Rodriguez-Fraticelli1,2,3,4, Caleb Weinreb5, Shou-Wen Wang5
1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
Nature
|July 17, 2020
概括
研究人员确定了一种分子特征,该特征是功能性的长期再生造血干细胞 (HSC). 转录因子TCF15对于HSC静止和自我更新至关重要,维持它们的再生能力.
科学领域:
- 干细胞生物学
- 血液形成
- 分子遗传学
背景情况:
- 造血干细胞具有对骨髓移植至关重要的终身再生能力.
- 在HSC中存在功能异质性,但底层机制尚不清楚.
- 单细胞RNA测序显示了转录的差异,但不能同时评估干细胞的功能.
研究的目的:
- 调查导致HSC功能异质性的分子机制.
- 在长期复制过程中同时分析HSC转录组和克隆轨迹.
- 确定与HSC自我更新和功能相关的内在分子程序.
主要方法:
- 实现可表达的lentiviral条形码,用于单个HSC的同时谱系和转录组分析.
- 分析了具有不同再生行为的HSC克隆之间的差异基因表达.
- 在体内使用CRISPR查以探测已识别的分子特征.
主要成果:
- 确定了一种内在的分子特征,
- 发现转录因子TCF15对于HSC静止和长期自我更新是必要和足够的.
- 证明TCF15表达标志着最原始的多功率HSC子集.
结论:
- 阐明了基底功能性HSC异质性的克隆内在分子程序.
- 确定TCF15是维持HSC自我更新状态的关键机制.
- 提供了对骨髓移植疗法至关重要的HSC再生能力的见解.
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