Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat

Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained...

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Main Authors: Ying Ye, Wenyan Xie, Zhaoru Ma, Xuepeng Wang, Yi Wen, Xuemei Li, Hongqian Qi, Hao Wu, Jinnan An, Yan Jiang, Xinyi Lu, Guokai Chen, Shijun Hu, Elizabeth A. Blaber, Xi Chen, Lei Chang, Wensheng Zhang
Format: Article
Language:English
Published: Nature Publishing Group 2024-02-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-024-01846-2
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author Ying Ye
Wenyan Xie
Zhaoru Ma
Xuepeng Wang
Yi Wen
Xuemei Li
Hongqian Qi
Hao Wu
Jinnan An
Yan Jiang
Xinyi Lu
Guokai Chen
Shijun Hu
Elizabeth A. Blaber
Xi Chen
Lei Chang
Wensheng Zhang
author_facet Ying Ye
Wenyan Xie
Zhaoru Ma
Xuepeng Wang
Yi Wen
Xuemei Li
Hongqian Qi
Hao Wu
Jinnan An
Yan Jiang
Xinyi Lu
Guokai Chen
Shijun Hu
Elizabeth A. Blaber
Xi Chen
Lei Chang
Wensheng Zhang
author_sort Ying Ye
collection DOAJ
description Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.
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spelling doaj.art-4eb06d043c0344e8b17d30e399cd63052024-03-05T17:41:49ZengNature Publishing GroupCell Death Discovery2058-77162024-02-0110111410.1038/s41420-024-01846-2Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostatYing Ye0Wenyan Xie1Zhaoru Ma2Xuepeng Wang3Yi Wen4Xuemei Li5Hongqian Qi6Hao Wu7Jinnan An8Yan Jiang9Xinyi Lu10Guokai Chen11Shijun Hu12Elizabeth A. Blaber13Xi Chen14Lei Chang15Wensheng Zhang16Medical College of Soochow UniversityMedical College of Soochow UniversityMedical College of Soochow UniversityMedical College of Soochow UniversityShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and TechnologySchool of Basic Medical Sciences, Binzhou Medical UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai University, TianjinMedical College of Soochow UniversityInstitute of Blood and Marrow Transplantation, Medical College of Soochow UniversitySchool of Biology and Basic Medical Sciences, Medical College of Soochow UniversityState Key Laboratory of Medicinal Chemical Biology, Nankai University, TianjinCentre of Reproduction, Development and Aging, Faculty of Health Sciences, University of MacauDepartment of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Medical College of Soochow UniversityDepartment of Biomedical Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic InstituteShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and TechnologyState Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Jiangsu Province International Joint Laboratory For Regeneration Medicine, Medical College of Soochow UniversityMedical College of Soochow UniversityAbstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.https://doi.org/10.1038/s41420-024-01846-2
spellingShingle Ying Ye
Wenyan Xie
Zhaoru Ma
Xuepeng Wang
Yi Wen
Xuemei Li
Hongqian Qi
Hao Wu
Jinnan An
Yan Jiang
Xinyi Lu
Guokai Chen
Shijun Hu
Elizabeth A. Blaber
Xi Chen
Lei Chang
Wensheng Zhang
Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
Cell Death Discovery
title Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
title_full Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
title_fullStr Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
title_full_unstemmed Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
title_short Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat
title_sort conserved mechanisms of self renewal and pluripotency in mouse and human escs regulated by simulated microgravity using a 3d clinostat
url https://doi.org/10.1038/s41420-024-01846-2
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