Etv5 safeguards trophoblast stem cells differentiation from mouse EPSCs by regulating fibroblast growth factor receptor
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ORIGINAL ARTICLE
Etv5 safeguards trophoblast stem cells differentiation from mouse EPSCs by regulating fibroblast growth factor receptor 2 Kui Zhu1 · Yuan Liu1 · Chen Fan1 · Mengyao Zhang1 · Hongxia Cao1 · Xin He1 · Na Li1 · Dianfeng Chu2 · Fang Li2 · Min Zou2 · Jinlian Hua1 · Huayan Wang1 · Yan Wang1 · Gencheng Fan2 · Shiqiang Zhang1 Received: 12 June 2020 / Revised: 29 October 2020 / Accepted: 31 October 2020 © Springer Nature B.V. 2020
Abstract Previous studies have demonstrated that transcription factor Etv5 plays an important role in the segregation between epiblast and primitive endoderm at the second fate decision of early embryo. However, it remains elusive whether Etv5 functions in the segregation between inner cell mass and trophectoderm at the first cell fate decision. In this study, we firstly generated Etv5 knockout mouse embryonic stem cells (mESCs) by CRISPR/Cas9, then converted them into extended potential stem cells (EPSCs) by culturing the cells in small molecule cocktail medium LCDM (LIF, CHIR99021, (S)-(+)-dimethindene maleate, minocycline hydrochloride), and finally investigated their differentiation efficiency of trophoblast stem cells (TSCs). The results showed that Etv5 knockout significantly decreased the efficiency of TSCs ( CDX2+) differentiated from EPSCs. In addition, Etv5 knockout resulted in higher incidence of the differentiated cells with tetraploid and octoploid than that from wild type. Mechanistically, Etv5 was activated by extracellular-signal-regulated kinase (ERK) signaling pathway; in turn, Etv5 had a positive feedback on the expression of fibroblast growth factor receptor 2 (FGFR2) which lies upstream of ERK. Etv5 knockout decreased the expression of FGFR2, whose binding with fibroblast growth factor 4 was essentially needed for TSCs differentiation. Collectively, the findings in this study suggest that Etv5 is required to safeguard the TSCs differentiation by regulating FGFR2 and provide new clues to understand the specification of trophectoderm in vivo. Keywords Etv5 · Mouse embryonic stem cells · Extended potential stem cells · Trophoblast stem cells · Fibroblast growth factor receptor 2
Kui Zhu and Yuan Liu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05969-4) contains supplementary material, which is available to authorized users. * Gencheng Fan [email protected]
Fang Li [email protected]
* Shiqiang Zhang [email protected]
Min Zou [email protected]
Kui Zhu [email protected]
Yan Wang [email protected]
Yuan Liu [email protected]
1
College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering and Technology, Northwest A&F University, 712100 Yangling, China
2
State Key Laboratory of Genetically Engineered Veterinary Vaccines, Yebio Bioengineering Co.Ltd of Qingdao, Qingdao, China
Mengyao Zhang [email protected] Xin He [email protected] Na Li [email protected]
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Vol.:(0123456789)
Molecular Biolog
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