The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice
Trophoblasts are the first cell type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not...
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MDPI AG
2020-03-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/4/840 |
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| author | Mariyan J. Jeyarajah Gargi Jaju Bhattad Dendra M. Hillier Stephen J. Renaud |
| author_facet | Mariyan J. Jeyarajah Gargi Jaju Bhattad Dendra M. Hillier Stephen J. Renaud |
| author_sort | Mariyan J. Jeyarajah |
| collection | DOAJ |
| description | Trophoblasts are the first cell type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription factor OVO-like 2 (OVOL2) fail to produce a functioning placenta, and die around embryonic day 10.5, suggesting that OVOL2 may be critical for trophoblast development. Therefore, our objective was to determine the role of OVOL2 in mouse TS cell fate. We found that OVOL2 was highly expressed in mouse placenta and differentiating TS cells. Placentas and TS cells lacking OVOL2 showed poor trophoblast differentiation potential, including increased expression of stem-state associated genes (<i>Eomes, Esrrb, Id2</i>) and decreased levels of differentiation-associated transcripts (<i>Gcm1</i>, <i>Tpbpa, Prl3b1, Syna</i>). Ectopic OVOL2 expression in TS cells elicited precocious differentiation. OVOL2 bound proximate to the gene encoding inhibitor of differentiation 2 (ID2), a dominant negative helix-loop-helix protein, and directly repressed its activity. Overexpression of ID2 was sufficient to reinforce the TS cell stem state. Our findings reveal a critical role of OVOL2 as a regulator of TS cell differentiation and placental development, in-part by coordinating repression of ID2. |
| first_indexed | 2024-03-10T20:47:00Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T20:47:00Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-8bb8688f5607448188b9ea20abc2a5852023-11-19T20:14:05ZengMDPI AGCells2073-44092020-03-019484010.3390/cells9040840The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in MiceMariyan J. Jeyarajah0Gargi Jaju Bhattad1Dendra M. Hillier2Stephen J. Renaud3Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaTrophoblasts are the first cell type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription factor OVO-like 2 (OVOL2) fail to produce a functioning placenta, and die around embryonic day 10.5, suggesting that OVOL2 may be critical for trophoblast development. Therefore, our objective was to determine the role of OVOL2 in mouse TS cell fate. We found that OVOL2 was highly expressed in mouse placenta and differentiating TS cells. Placentas and TS cells lacking OVOL2 showed poor trophoblast differentiation potential, including increased expression of stem-state associated genes (<i>Eomes, Esrrb, Id2</i>) and decreased levels of differentiation-associated transcripts (<i>Gcm1</i>, <i>Tpbpa, Prl3b1, Syna</i>). Ectopic OVOL2 expression in TS cells elicited precocious differentiation. OVOL2 bound proximate to the gene encoding inhibitor of differentiation 2 (ID2), a dominant negative helix-loop-helix protein, and directly repressed its activity. Overexpression of ID2 was sufficient to reinforce the TS cell stem state. Our findings reveal a critical role of OVOL2 as a regulator of TS cell differentiation and placental development, in-part by coordinating repression of ID2.https://www.mdpi.com/2073-4409/9/4/840embryogenesisblastocysttranscriptional repressiontrophoblast stem cellstrophoblast differentiationplacenta |
| spellingShingle | Mariyan J. Jeyarajah Gargi Jaju Bhattad Dendra M. Hillier Stephen J. Renaud The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice Cells embryogenesis blastocyst transcriptional repression trophoblast stem cells trophoblast differentiation placenta |
| title | The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice |
| title_full | The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice |
| title_fullStr | The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice |
| title_full_unstemmed | The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice |
| title_short | The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice |
| title_sort | transcription factor ovol2 represses id2 and drives differentiation of trophoblast stem cells and placental development in mice |
| topic | embryogenesis blastocyst transcriptional repression trophoblast stem cells trophoblast differentiation placenta |
| url | https://www.mdpi.com/2073-4409/9/4/840 |
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