Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming

Sergio Ruiz, Athurva Gore, Zhe Li, Athanasia D. Panopoulos, Nuria Montserrat, Ho-Lim Fung, Alessandra Giorgetti, Josipa Bilic, Erika M. Batchelder, Holm Zaehres, Hans R. Schöler, Kun Zhang () and Juan Carlos Izpisua Belmonte ()
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Sergio Ruiz: Gene Expression Laboratory, Salk Institute for Biological Studies
Athurva Gore: University of California at San Diego
Zhe Li: University of California at San Diego
Athanasia D. Panopoulos: Gene Expression Laboratory, Salk Institute for Biological Studies
Nuria Montserrat: Center of Regenerative Medicine in Barcelona
Ho-Lim Fung: University of California at San Diego
Alessandra Giorgetti: Center of Regenerative Medicine in Barcelona
Josipa Bilic: Center of Regenerative Medicine in Barcelona
Erika M. Batchelder: Gene Expression Laboratory, Salk Institute for Biological Studies
Holm Zaehres: Max Planck Institute for Molecular Biomedicine
Hans R. Schöler: Max Planck Institute for Molecular Biomedicine
Kun Zhang: University of California at San Diego
Juan Carlos Izpisua Belmonte: Gene Expression Laboratory, Salk Institute for Biological Studies

Nature Communications, 2013, vol. 4, issue 1, 1-8

Abstract: Abstract Recent studies indicate that human-induced pluripotent stem cells contain genomic structural variations and point mutations in coding regions. However, these studies have focused on fibroblast-derived human induced pluripotent stem cells, and it is currently unknown whether the use of alternative somatic cell sources with varying reprogramming efficiencies would result in different levels of genetic alterations. Here we characterize the genomic integrity of eight human induced pluripotent stem cell lines derived from five different non-fibroblast somatic cell types. We show that protein-coding mutations are a general feature of the human induced pluripotent stem cell state and are independent of somatic cell source. Furthermore, we analyse a total of 17 point mutations found in human induced pluripotent stem cells and demonstrate that they do not generally facilitate the acquisition of pluripotency and thus are not likely to provide a selective advantage for reprogramming.

Date: 2013
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DOI: 10.1038/ncomms2381

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