title: The reprogramming factor nuclear receptor subfamily 5, group A, member 2 cannot replace octamer-binding transcription factor 4 function in the self-renewal of embryonic stem cells.
abstract: Although octamer-binding transcription factor 4 (Oct-4) is one of the most intensively studied factors in mammalian development, no cellular genes capable of replacing Oct-4 function in embryonic stem (ES) cells have been found. Recent data show that nuclear receptor subfamily 5, group A, member 2 (Nr5a2) is able to replace Oct-4 function in the reprogramming process; however, it is unclear whether Nr5a2 can replace Oct-4 function in ES cells. In this study, the ability of Nr5a2 to maintain self-renewal and pluripotency in ES cells was investigated. Nr5a2 localized to the nucleus in ES cells, similarly to Oct-4. However, expression of Nr5a2 failed to rescue the stem cell phenotype or to maintain the self-renewal ability of ES cells. Furthermore, as compared with Oct-4-expressing ES cells, Nr5a2-expressing ES cells showed a reduced number of cells in S-phase, did not expand normally, and did not remain in an undifferentiated state. Ectopic expression of Nr5a2 in ES cells was not able to activate transcription of ES cell-specific genes, and gene expression profiling demonstrated differences between Nr5a2-expressing and Oct-4-expressing ES cells. In addition, Nr5a2-expressing ES cells were not able to form teratomas in nude mice. Taken together, these results strongly suggest that the gene regulation properties of Nr5a2 and Oct-4 and their abilities to confer self-renewal and pluripotency of ES cells differ. The present study provides strong evidence that Nr5a2 cannot replace Oct-4 function in ES cells.
authors.affiliation: Department of Life Science, Laboratory of Molecular and Cellular Biology, Sogang University, Seoul, Korea.
authors.forename: Kyeng-Won
authors.initials: KW
authors.lastname: Choi
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Oh
authors.forename: Jaeyoung
authors.initials: J
authors.lastname: Lee
authors.forename: Bobae
authors.initials: B
authors.lastname: Lim
authors.forename: Yong-Mahn
authors.initials: YM
authors.lastname: Han
authors.forename: Junseo
authors.initials: J
authors.lastname: Oh
authors.forename: Jungho
authors.initials: J
authors.lastname: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*
chemical_list: C431936:Nr5a2 protein, mouse; D050814:Octamer Transcription Factor-3; D018160:Receptors, Cytoplasmic and Nuclear
keywords: embryonic stem cell; induced pluripotent stem cell; nuclear receptor subfamily 5, group A, member 2 (Nr5a2); octamer-binding transcription factor 4 (Oct-4); self-renewal