身体表皮突变使得单细胞血统的追踪能够在鼠和人类的寿命中进行本地血液形成
Michael Scherer1, Indranil Singh2, Martina Braun1
1Computational Biology and Health Genomics, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08003 Barcelona, Spain.
bioRxiv : the preprint server for biology
|April 15, 2024
概括
EPI-克隆使用DNA甲基化来追踪干细胞血统而无需基因工程. 这种方法准确地绘制了单细胞中的数百个克隆轨迹,揭示了对衰老和克隆动态的洞察力.
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.
- 血液形成 血液形成 血液形成
背景情况:
- 目前的谱系追踪方法通常需要基因修饰或与单细胞分辨率作斗争.
- 稀少的体质DNA变异很难捕获用于全面的克隆分析.
研究的目的:
- 开发一种无转基因的方法,用于高分辨率的单细胞血统追踪.
- 研究血液形成中的克隆动力学,特别是在衰老过程中.
主要方法:
- 开发了EPI-克隆,一种以滴滴为基础的技术,以单个CpG分辨率进行单细胞DNA甲基化分析.
- 应用EPI-克隆对来自小鼠和人类造血系统的近10万个单细胞进行分析.
- 经过验证的EPI-克隆精度使用基因条形码.
主要成果:
- EPI-克隆精确地识别出克隆系在造血分化的过程中.
- 观察到老鼠的克隆复杂性随着年龄的增长而下降,并扩展了罕见的干细胞克隆.
- 在老年人中鉴定出扩张的造血克隆,有或没有遗传病变.
结论:
- EPI-克隆提供准确,无转基因和可扩展的单细胞血统追踪.
- 该方法为干细胞的克隆动态和衰老提供了新的见解.
- 能够详细分析血液造血干细胞在健康和疾病中的行为.
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