Mouse SCNT ESCs Have Lower Somatic Mutation Load Than Syngeneic iPSCs

• Comparison of somatic-coding mutation load in SCNT ESCs and iPSCs in mice
• Lower mutational load in SCNT ESCs than iPSCs of syngeneic background

SummaryEctopic expression of reprogramming factors has been widely adopted to reprogram somatic nucleus into a pluripotent state (induced pluripotent stem cells [iPSCs]). However, genetic aberrations such as somatic gene mutation in the resulting iPSCs have raised concerns regarding their clinical utility. To test whether the increased somatic mutations are primarily the by-products of current reprogramming methods, we reprogrammed embryonic fibroblasts of inbred C57BL/6 mice into either iPSCs (8 lines, 4 previously published) or embryonic stem cells (ESCs) with somatic cell nuclear transfer (SCNT ESCs; 11 lines). Exome sequencing of these lines indicates a significantly lower mutation load in SCNT ESCs than iPSCs of syngeneic background. In addition, one SCNT-ESC line has no detectable exome mutation, and two pairs of SCNT-ESC lines only have shared preexisting mutations. In contrast, every iPSC line carries unique mutations. Our study highlights the need for improving reprogramming methods in more physiologically relevant conditions.

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