ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2
Porcine-induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell preclinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor estrogen-related receptor beta (ESRRB), was poorly understood. Her...
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doaj-c38c65620fa040af84101237e46df3712021-09-20T05:20:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-09-01910.3389/fcell.2021.712224712224ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2Shuai Yu0Rui Zhang1Qiaoyan Shen2Zhenshuo Zhu3Juqing Zhang4Xiaolong Wu5Wenxu Zhao6Na Li7Fan Yang8Hongjiang Wei9Jinlian Hua10College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaKey Laboratory of Animal Gene Editing and Animal Cloning in Yunnan Province, Yunnan Agricultural University, Kunming, ChinaCollege of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering and Technology, Northwest A&F University, Shaanxi, ChinaPorcine-induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell preclinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor estrogen-related receptor beta (ESRRB), was poorly understood. Here, we constructed ESRRB-overexpressing piPSCs (ESRRB-piPSCs). Compared with the control piPSCs (CON-piPSCs), the ESRRB-piPSCs showed flat, monolayered colony morphology. Moreover, the ESRRB-piPSCs showed greater chimeric capacity into trophectoderm than CON-piPSCs. We found that ESRRB could directly regulate the expressions of trophoblast stem cell (TSC)-specific markers, including KRT8, KRT18 and CDX2, through binding to their promoter regions. Mutational analysis proved that the N-terminus zinc finger domain is indispensable for ESRRB to regulate the TSC markers. Furthermore, this regulation needs the participation of OCT4. Accordingly, the cooperation between ESRRB and OCT4 facilitates the conversion from pluripotent state to the trophoblast-like state. Our results demonstrated a unique and crucial role of ESRRB in determining piPSCs fate, and shed new light on the molecular mechanism underlying the segregation of embryonic and extra-embryonic lineages.https://www.frontiersin.org/articles/10.3389/fcell.2021.712224/fullESRRBKRT8Cdx2induced pluripotent stem cells (iPSCs)trophoblast stem cells (TSCs) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuai Yu Rui Zhang Qiaoyan Shen Zhenshuo Zhu Juqing Zhang Xiaolong Wu Wenxu Zhao Na Li Fan Yang Hongjiang Wei Jinlian Hua |
spellingShingle |
Shuai Yu Rui Zhang Qiaoyan Shen Zhenshuo Zhu Juqing Zhang Xiaolong Wu Wenxu Zhao Na Li Fan Yang Hongjiang Wei Jinlian Hua ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 Frontiers in Cell and Developmental Biology ESRRB KRT8 Cdx2 induced pluripotent stem cells (iPSCs) trophoblast stem cells (TSCs) |
author_facet |
Shuai Yu Rui Zhang Qiaoyan Shen Zhenshuo Zhu Juqing Zhang Xiaolong Wu Wenxu Zhao Na Li Fan Yang Hongjiang Wei Jinlian Hua |
author_sort |
Shuai Yu |
title |
ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 |
title_short |
ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 |
title_full |
ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 |
title_fullStr |
ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 |
title_full_unstemmed |
ESRRB Facilitates the Conversion of Trophoblast-Like Stem Cells From Induced Pluripotent Stem Cells by Directly Regulating CDX2 |
title_sort |
esrrb facilitates the conversion of trophoblast-like stem cells from induced pluripotent stem cells by directly regulating cdx2 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cell and Developmental Biology |
issn |
2296-634X |
publishDate |
2021-09-01 |
description |
Porcine-induced pluripotent stem cells (piPSCs) could serve as a great model system for human stem cell preclinical research. However, the pluripotency gene network of piPSCs, especially the function for the core transcription factor estrogen-related receptor beta (ESRRB), was poorly understood. Here, we constructed ESRRB-overexpressing piPSCs (ESRRB-piPSCs). Compared with the control piPSCs (CON-piPSCs), the ESRRB-piPSCs showed flat, monolayered colony morphology. Moreover, the ESRRB-piPSCs showed greater chimeric capacity into trophectoderm than CON-piPSCs. We found that ESRRB could directly regulate the expressions of trophoblast stem cell (TSC)-specific markers, including KRT8, KRT18 and CDX2, through binding to their promoter regions. Mutational analysis proved that the N-terminus zinc finger domain is indispensable for ESRRB to regulate the TSC markers. Furthermore, this regulation needs the participation of OCT4. Accordingly, the cooperation between ESRRB and OCT4 facilitates the conversion from pluripotent state to the trophoblast-like state. Our results demonstrated a unique and crucial role of ESRRB in determining piPSCs fate, and shed new light on the molecular mechanism underlying the segregation of embryonic and extra-embryonic lineages. |
topic |
ESRRB KRT8 Cdx2 induced pluripotent stem cells (iPSCs) trophoblast stem cells (TSCs) |
url |
https://www.frontiersin.org/articles/10.3389/fcell.2021.712224/full |
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