A promising iPS-based single-cell cloning strategy revealing signatures of somatic mutations in heterogeneous normal cells

A promising iPS-based single-cell cloning strategy revealing signatures of somatic mutations in heterogeneous normal cells
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一种有前景的基于 iPS 的单细胞克隆策略,揭示异质正常细胞中体细胞突变的特征

DOI:
10.1016/j.csbj.2020.08.026
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发表时间:
2020-09
影响因子:
6
通讯作者:
Cai Jun
Cai Jun
中科院分区:
生物学2区
文献类型:
--
作者:
Miao Xuexia;Li Yueying;Zheng Caihong;Wang Lifei;Jin Chen;Chen Lei;Mi Shuangli;Zhai Weiwei;Wang Qian-Fei;Cai Jun

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随着微量DNA扩增技术的发展,单细胞基因组学迅速发展。然而,目前的技术受到各种陷阱的影响,如污染、基因组覆盖不均匀和扩增错误。即使对于单个干细胞来源的克隆形成的“黄金”策略,高保真扩增也仅适用于单个干细胞。准确定义不同细胞类型中单个细胞的体细胞突变仍然是具有挑战性的。在此,我们首次提供了证据,证明诱导的多能干细胞(iPS细胞或IPSC)作为单个体细胞来源的克隆,记录的突变图谱与初始细胞前体几乎相同(>90%)。这一发现表明,iPS技术适用于任何细胞类型,可以作为一种有利于单细胞基因组扩增的细胞克隆策略。这一新的策略不受细胞类型限制或扩增伪影的限制,从而使我们能够详细研究异种正常细胞的体细胞突变特征。
Single-cell genomics has advanced rapidly as trace-DNA amplification technologies evolved. However, current technologies are subject to a variety of pitfalls such as contamination, uneven genomic coverage, and amplification errors. Even for the “golden” strategy of single stem cell-derived clonal formation, high-fidelity amplification is applicable merely to single stem cells. It’s still challenging to accurately define somatic mutations of a single cell in various cell types. Herein, we provided evidence, for the first time, to prove that induced pluripotent stem cells (iPS cells or iPSC), being a single somatic cell-derived clone, are recording almost identical (>90%) mutational profile of the initial cell progenitor. This finding demonstrates iPS technique, applicable to any cell type, can be utilized as a cell cloning strategy favorable for single-cell genomic amplification. This novel strategy is not limited by cell-type constraints or amplification artifacts, and thus enables our detailed investigation on the characteristics of somatic mutations in heterogeneous normal cells.
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