Genetic Heterogeneity of Induced Pluripotent Stem Cells: Exome sequence of 24 clones derived from a single mouse. Mus musculus

Induced pluripotent stem cells (iPSCs), created by reprogramming somatic cells to a pluripotent state, are a potentially powerful tool for modeling disease and treatment. As the generation of an iPSC starts with a single somatic cell, all of the cells in the resulting iPSC clone would be expected to carry forward the genetic variants of the founding cell. We have observed the genetic heterogeneity resulting from the cloning of individual cells in a previous study with a small number of clones derived from multiple mouse strains. To more comprehensively assess the degree of genetic heterogeneity that can result from iPSC generation and to determine whether some cells are more genetically 'fit' for reprogramming, we have performed exome sequencing via two capture platforms on 24 mouse iPSC clones derived from skin fibroblasts obtained from two different sites on the same 8-week-old C57BL/6J male mouse.

诱导多能干细胞（induced pluripotent stem cells，iPSCs）是通过将体细胞（somatic cells）重编程（reprogramming）至多能状态（pluripotent state）而获得的细胞类型，在疾病建模与治疗研究中拥有极具潜力的应用价值。由于iPSC的构建起始于单个体细胞，理论上最终生成的iPSC克隆中的所有细胞均应携带该创始细胞（founding cell）的全部遗传变异（genetic variants）。在既往一项针对多品系小鼠来源的少量克隆的研究中，我们已观测到单细胞克隆过程所引发的遗传异质性（genetic heterogeneity）。为更全面地评估iPSC构建过程中可能产生的遗传异质性程度，并探究是否存在某些细胞在重编程方面具备更优的遗传适配性，我们采用两种外显子捕获平台（exome capture platform），对取自同一只8周龄雄性C57BL/6J小鼠两处不同皮肤位点的皮肤成纤维细胞（skin fibroblasts）所构建的24个小鼠iPSC克隆开展了外显子组测序（exome sequencing）。