Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal

Dax1(also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax...

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Main Authors: Jianrong He, Yuda Cheng, Yan Ruan, Jiali Wang, Yanping Tian, Jiaqi Wang, Fengsheng Wang, Chen Zhang, Yixiao Xu, Lianlian Liu, Meng Yu, Jiangjun Wang, Binyu Zhao, Yue Zhang, Yi Yang, Gaoke Liu, Wei Wu, Ping He, Jiaxiang Xiong, He Huang, Junlei Zhang, Rui Jian
Format: Article
Language:English
Published: Hindawi Limited 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/5522723
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spelling doaj-10377facd0ba46299acaa6213344b66d2021-07-19T01:04:00ZengHindawi LimitedStem Cells International1687-96782021-01-01202110.1155/2021/5522723Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-RenewalJianrong He0Yuda Cheng1Yan Ruan2Jiali Wang3Yanping Tian4Jiaqi Wang5Fengsheng Wang6Chen Zhang7Yixiao Xu8Lianlian Liu9Meng Yu10Jiangjun Wang11Binyu Zhao12Yue Zhang13Yi Yang14Gaoke Liu15Wei Wu16Ping He17Jiaxiang Xiong18He Huang19Junlei Zhang20Rui Jian21Department of AnesthesiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyExperimental Center of Basic MedicineLaboratory of Stem Cell & Developmental BiologyThoracic Surgery DepartmentCardiac Surgery DepartmentExperimental Center of Basic MedicineDepartment of AnesthesiologyLaboratory of Stem Cell & Developmental BiologyLaboratory of Stem Cell & Developmental BiologyDax1(also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most proapoptotic genes and lineage-commitment genes were drastically increased, while the downregulated expression of antiapoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.http://dx.doi.org/10.1155/2021/5522723
collection DOAJ
language English
format Article
sources DOAJ
author Jianrong He
Yuda Cheng
Yan Ruan
Jiali Wang
Yanping Tian
Jiaqi Wang
Fengsheng Wang
Chen Zhang
Yixiao Xu
Lianlian Liu
Meng Yu
Jiangjun Wang
Binyu Zhao
Yue Zhang
Yi Yang
Gaoke Liu
Wei Wu
Ping He
Jiaxiang Xiong
He Huang
Junlei Zhang
Rui Jian
spellingShingle Jianrong He
Yuda Cheng
Yan Ruan
Jiali Wang
Yanping Tian
Jiaqi Wang
Fengsheng Wang
Chen Zhang
Yixiao Xu
Lianlian Liu
Meng Yu
Jiangjun Wang
Binyu Zhao
Yue Zhang
Yi Yang
Gaoke Liu
Wei Wu
Ping He
Jiaxiang Xiong
He Huang
Junlei Zhang
Rui Jian
Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
Stem Cells International
author_facet Jianrong He
Yuda Cheng
Yan Ruan
Jiali Wang
Yanping Tian
Jiaqi Wang
Fengsheng Wang
Chen Zhang
Yixiao Xu
Lianlian Liu
Meng Yu
Jiangjun Wang
Binyu Zhao
Yue Zhang
Yi Yang
Gaoke Liu
Wei Wu
Ping He
Jiaxiang Xiong
He Huang
Junlei Zhang
Rui Jian
author_sort Jianrong He
title Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
title_short Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
title_full Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
title_fullStr Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
title_full_unstemmed Pluripotency-State-Dependent Role of Dax1 in Embryonic Stem Cells Self-Renewal
title_sort pluripotency-state-dependent role of dax1 in embryonic stem cells self-renewal
publisher Hindawi Limited
series Stem Cells International
issn 1687-9678
publishDate 2021-01-01
description Dax1(also known as Nr0b1) is regarded as an important component of the transcription factor network in mouse embryonic stem cells (ESCs). However, the role and the molecular mechanism of Dax1 in the maintenance of different pluripotency states are poorly understood. Here, we constructed a stable Dax1 knockout (KO) cell line using the CRISPR/Cas9 system to analyze the precise function of Dax1. We reported that 2i/LIF-ESCs had significantly lower Dax1 expression than LIF/serum-ESCs. Dax1KO ES cell lines could be established in 2i/LIF and their pluripotency was confirmed. In contrast, Dax1-null ESCs could not be continuously passaged in LIF/serum due to severe differentiation and apoptosis. In LIF/serum, the activities of the Core module and Myc module were significantly reduced, while the PRC2 module was activated after Dax1KO. The expression of most proapoptotic genes and lineage-commitment genes were drastically increased, while the downregulated expression of antiapoptotic genes and many pluripotency genes was observed. Our research on the pluripotent state-dependent role of Dax1 provides clues to understand the molecular regulation mechanism at different stages of early embryonic development.
url http://dx.doi.org/10.1155/2021/5522723
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