Induction of Pluripotent Stem Cells from Primordial Germ Cells by Single Reprogramming Factors§

Authors


  • Author contributions: G.N.: conception and design, collection and assembly of data, data analysis and interpretation, and manuscript writing.; T. Kosaka: conception and design, collection and assembly of data, and data analysis and interpretation; S.S.: performed informatics analysis of microarray data; H.H.: generated and analyzed the chimeric mice of mPGCs; K.T.: conception and design and data analysis and interpretation.; T. Kinoshita: collection and assembly of data and data analysis and interpretation; H.A. and T. Sudo: performed the microarray experiments; K.H.: performed informatics analysis of the microarray data; M.O.: administrative support and data analysis and interpretation; T. Suda: conception and design, financial support, administrative support, data analysis and interpretation, and final approval of the manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS December 19, 2012.

Abstract

Germ cells are similar to pluripotent stem cells in terms of gene expression patterns and the capacity to convert to pluripotent stem cells in culture. The factors involved in germ cell development are also able to reprogram somatic cells. This suggests that germ cells are useful tools for investigating the mechanisms responsible for somatic cell reprograming. In this study, the expression of reprograming factors in primordial germ cells (PGCs) was analyzed. PGCs expressed Oct3/4, Sox2, and c-Myc but not Klf4. However, Klf2, Klf5, Essrb, or Essrg, which were expressed in PGCs, could compensate for Klf4 during somatic cell reprograming. Furthermore, PGCs could be converted to a pluripotent state by infection with any of the known reprogramming factors (Oct3/4, Sox2, Klf4, and c-Myc). These cells were designated as multipotent PGCs (mPGCs). Contrary to differences in the origins of somatic cells in somatic cell reprogramming, we hypothesized that the gene expression levels of the reprogramming factors would vary in mPGCs. Candidate genes involved in the regulation of tumorigenicity and/or reprogramming efficiency were identified by comparing the gene expression profiles of mPGCs generated by the exogenous expression of c-Myc or L-Myc. STEM CELLS2013;31:479–487

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