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: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/5522723
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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
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
collection DOAJ
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.
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spelling doaj-art-10377facd0ba46299acaa6213344b66d2025-02-03T01:04:18ZengWileyStem Cells International1687-966X1687-96782021-01-01202110.1155/2021/55227235522723Pluripotency-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 Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaExperimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaThoracic Surgery Department, Southwest Hospital, The First Hospital Affiliated to Army Medical University, Chongqing 400038, ChinaCardiac Surgery Department, Southwest Hospital, The First Hospital Affiliated to Army Medical University, Chongqing 400038, ChinaExperimental Center of Basic Medicine, College of Basic Medical Sciences, Army Medical University, Chongqing 400038, ChinaDepartment of Anesthesiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaLaboratory of Stem Cell & Developmental Biology, Department of Histology and Embryology, Army Medical University, Chongqing 400038, ChinaDax1(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
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
title 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_short 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
url http://dx.doi.org/10.1155/2021/5522723
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