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.
| Original language | English |
|---|---|
| Pages (from-to) | 1029-1045 |
| Number of pages | 17 |
| Journal | FEBS Journal |
| Volume | 281 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 Feb 1 |
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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
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
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. / Choi, Kyeng Won; Oh, Hye Rim; Lee, Jaeyoung; Lim, Bobae; Han, Yong Mahn; Oh, Jun Seo; Kim, Jungho.
In: FEBS Journal, Vol. 281, No. 4, 01.02.2014, p. 1029-1045.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Choi, Kyeng Won
AU - Oh, Hye Rim
AU - Lee, Jaeyoung
AU - Lim, Bobae
AU - Han, Yong Mahn
AU - Oh, Jun Seo
AU - Kim, Jungho
PY - 2014/2/1
Y1 - 2014/2/1
N2 - 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.
AB - 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.
KW - embryonic stem cell
KW - induced pluripotent stem cell
KW - nuclear receptor subfamily 5, group A, member 2 (Nr5a2)
KW - octamer-binding transcription factor 4 (Oct-4)
KW - self-renewal
UR - http://www.scopus.com/inward/record.url?scp=84894286159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84894286159&partnerID=8YFLogxK
U2 - 10.1111/febs.12665
DO - 10.1111/febs.12665
M3 - Article
VL - 281
SP - 1029
EP - 1045
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 4
ER -