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.

随着痕量DNA扩增技术的发展，单细胞基因组学发展迅速。但是，当前的技术容易受到各种陷阱的影响，例如污染，基因组覆盖率不均匀以及扩增错误。即使是单干细胞衍生克隆形成的“黄金”策略，高保真扩增也仅适用于单干细胞。准确定义各种细胞类型中单个细胞的体细胞突变仍然具有挑战性。在此，我们首次提供了证据来证明诱导的多能干细胞（iPS细胞或iPSC）是单个体细胞来源的克隆，其记录的初始细胞祖细胞的突变谱几乎相同（> 90％） 。这一发现证明了iPS技术适用于任何类型的细胞，可以用作有利于单细胞基因组扩增的细胞克隆策略。这种新颖的策略不受细胞类型约束或扩增伪像的限制，因此使我们能够对异质正常细胞中体细胞突变的特征进行详细研究。