title: An integrated systems biology approach identifies positive cofactor 4 as a factor that increases reprogramming efficiency.
abstract: 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.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Jo
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Sohyun
authors.initials: S
authors.lastname: Hwang
authors.affiliation: CHA Stem Cell Institute, CHA University, Seoul, Korea.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea.
authors.forename: Soomin
authors.initials: S
authors.lastname: Hong
authors.affiliation: CHA Stem Cell Institute, CHA University, Seoul, Korea.
authors.forename: Jeoung Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: CHA Stem Cell Institute, CHA University, Seoul, Korea.
authors.forename: Sung-Geum
authors.initials: SG
authors.lastname: Lee
authors.affiliation: CHA Stem Cell Institute, CHA University, Seoul, Korea.
authors.forename: Ahmi
authors.initials: A
authors.lastname: Baek
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Heonjong
authors.initials: H
authors.lastname: Han
authors.affiliation: Fertility Center, CHA Gangnam Medical Center, College of Medicine, CHA University, Seoul, Korea.
authors.forename: Jin Il
authors.initials: JI
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea insuklee@yonsei.ac.kr.
authors.forename: Insuk
authors.initials: I
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea CHA Stem Cell Institute, CHA University, Seoul, Korea Fertility Center, CHA Gangnam Medical Center, College of Medicine, CHA University, Seoul, Korea drleedr@cha.ac.kr.
authors.forename: Dong Ryul
authors.initials: DR
authors.lastname: Lee
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics*; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D049490:Systems Biology / Q000379:methods; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489428:Myc protein, mouse; D009687:Nuclear Proteins; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; C056169:Rpo2tc1 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse; D014157:Transcription Factors