Spermatogonial stem cells (SSCs) can spontaneously dedifferentiate into embryonic stem cell (ESC)-like cells, which are designated as multipotent SSCs (mSSCs), without ectopic expression of reprogramming factors. Interestingly, SSCs express key pluripotency genes such asOct4,Sox2, Klf4 andMyc. Therefore, molecular dissection of mSSC reprogramming may provide clues about novel endogenous reprogramming or pluripotency regulatory factors. Our comparative transcriptome analysis of mSSCs and induced pluripotent stem cells (iPSCs) suggests that they have similar pluripotency states but are reprogrammed via different transcriptional pathways. We identified 53 genes as putative pluripotency regulatory factors using an integrated systems biology approach. We demonstrated a selected candidate, Positive cofactor 4 (Pc4), can enhance the efficiency of somatic cell reprogramming by promoting and maintaining transcriptional activity of the key reprograming factors. These results suggest that Pc4 has an important role in inducing spontaneous somatic cell reprogramming via up-regulation of key pluripotency genes.
Bibliographical noteFunding Information:
This research was partly supported by grants from the Bio and Medical Technology Development Program [2012M3A9C6049723] funded by the Ministry of Science, ICT and Future Planning, and Basic Science Research through the National Research Foundation ofKorea [2009- 0093821], the Stem Cell Research Program [2006-2004127 to D.L.], and grants from the National Research Foundation of Korea [2012M3A9B4028641, 2012M3A9C7050151 to I.L.]. Funding for open access charge: National Research Foundation of Korea.
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