Working Paper Article Version 1 This version is not peer-reviewed

The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice

Version 1 : Received: 6 March 2020 / Approved: 8 March 2020 / Online: 8 March 2020 (04:11:35 CET)

A peer-reviewed article of this Preprint also exists.

Jeyarajah, M.J.; Jaju Bhattad, G.; Hillier, D.M.; Renaud, S.J. The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice. Cells 2020, 9, 840. Jeyarajah, M.J.; Jaju Bhattad, G.; Hillier, D.M.; Renaud, S.J. The Transcription Factor OVOL2 Represses ID2 and Drives Differentiation of Trophoblast Stem Cells and Placental Development in Mice. Cells 2020, 9, 840.

Journal reference: Cells 2020, 9, 840
DOI: 10.3390/cells9040840

Abstract

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 (Eomes, Esrrb, Id2) and decreased levels of differentiation-associated transcripts (Gcm1, Tpbpa, Prl3b1, Syna). 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.

Subject Areas

embryogenesis; blastocyst; trophoblast; stem cell; differentiation; placenta; Ovo-like 2

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