Ye Ying, Xie Wenyan, Ma Zhaoru, Wang Xuepeng, Wen Yi, Li Xuemei, Qi Hongqian, Wu Hao, An Jinnan, Jiang Yan, Lu Xinyi, Chen Guokai, Hu Shijun, Blaber Elizabeth A, Chen Xi, Chang Lei, Zhang Wensheng
Medical College of Soochow University, Suzhou, China.
Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
Cell Death Discov. 2024 Feb 9;10(1):68. doi: 10.1038/s41420-024-01846-2.
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.
胚胎干细胞（ESCs）展现出无限自我更新和多能性的独特特性，使其在基础研究和临床应用中具有极高价值。以往关于微重力对胚胎干细胞自我更新和分化影响的研究主要停留在描述层面，受到实验机会和技术的限制。在本研究中，我们展示了来自小鼠和人类胚胎干细胞的有力证据，表明模拟微重力（SMG）诱导的应激通过一种此前未被识别的保守机制显著影响自我更新和多能性。具体而言，模拟微重力诱导热休克蛋白基因上调，进而增强核心多能性因子的表达并激活Wnt和/或LIF/STAT3信号通路，从而促进胚胎干细胞的自我更新。值得注意的是，在模拟微重力条件下，Tbx3上调促进Wnt通路活性增强，促使小鼠和人类胚胎干细胞向中内胚层分化。鉴于地面模拟微重力与真实微重力之间可能存在差异，未来的太空飞行实验对于验证低重力对胚胎干细胞自我更新和分化机制的影响至关重要。
