An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency

• Published in: Nucleic acids research 2016-02, Vol.44 (3), p.1203-1215
• Main Authors: Jo, Junghyun, Hwang, Sohyun, Kim, Hyung Joon, Hong, Soomin, Lee, Jeoung Eun, Lee, Sung-Geum, Baek, Ahmi, Han, Heonjong, Lee, Jin Il, Lee, Insuk, Lee, Dong Ryul
• Format: Article
• Language: English
• Subjects: Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Animals; Blotting, Western; Cells, Cultured; Cellular Reprogramming - genetics; Cluster Analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Profiling; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - metabolism; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Mice; Mice, Inbred C57BL; Molecular Biology; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; Reverse Transcriptase Polymerase Chain Reaction; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Systems Biology - methods; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkv1468

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 as Oct4, Sox2, Klf4 and Myc. 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.