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Updated: Jun 24, 2025

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通过单细胞共捕获DNA突变和mRNA转录的单细胞共捕获,对体内克隆马赛克的基因型与表型进行映射
Dennis J Yuan1,2,3, John Zinno1,2,3, Theo Botella1,2,3
1New York Genome Center, New York, NY.
bioRxiv : the preprint server for biology
|June 3, 2024
概括
衰老中的体质马赛克主义表明,驱动突变会影响细胞行为. 新的单细胞测序揭示了像NOTCH1和TP53这样的突变如何塑造老化组织中的克隆扩张和分化.
科学领域:
- 基因组学就是基因组学.
- 细胞生物学 细胞生物学
- 衰老研究研究 衰老研究
背景情况:
- 在衰老和癌症中常见的体质马赛克主义,涉及具有突变的细胞克隆.
- 目前的批量测序方法限制了对克隆架构和突变共发生的理解.
- 特定细胞克隆内驱动突变的表型后果仍然不太清楚.
研究的目的:
- 开发一种联合单细胞分析体位突变和mRNA的方法.
- 在固体组织体质马赛克中重建克隆架构和相关的表型.
- 研究驱动突变对老年人组织细胞行为的影响.
主要方法:
- 开发了单细胞基因型到表型 (scG2P) 测序.
- 从单个细胞中高通量,复合捕获基因组区域和mRNA标记物.
- 将scG2P应用于高酒精/烟草暴露率的个体的老化食道样本.
主要成果:
- 观察到一个克隆格局,以单驱动事件克隆为主,罕见的双驱动克隆.
- NOTCH1突变是普遍存在的,并与表皮分化受损相关.
- TP53突变和双驱动突变通过分化偏差和细胞循环表现出增加的克隆扩张.
结论:
- 对突变和转录的联合单细胞捕获使得克隆结构的高分辨率重建成为可能.
- 驱动突变显著影响细胞表型,包括分化和增殖.
- scG2P是研究衰老和疾病中的体质马赛克主义的强大工具.
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