Timilsina S, Kirsch-Mangu T, Werth S, Shepard B, Ma T, Villa-Diaz L G
Department of Biological Sciences, Oakland University, Rochester, MI, 48309, USA.
Department of Computer Science, Engineering, Oakland University, Rochester, MI, 48309, USA.
NPJ Microgravity. 2022 Jul 4;8(1):22. doi: 10.1038/s41526-022-00209-4.
A systematic study on the biological effects of simulated microgravity (sµg) on human pluripotent stem cells (hPSC) is still lacking. Here, we used a fast-rotating 2-D clinostat to investigate the sµg effect on proliferation, self-renewal, and cell cycle regulation of hPSCs. We observed significant upregulation of protein translation of pluripotent transcription factors in hPSC cultured in sµg compared to cells cultured in 1g conditions. In addition to a significant increase in expression of telomere elongation genes. Differentiation experiments showed that hPSC cultured in sµg condition were less susceptible to differentiation compared to cells in 1g conditions. These results suggest that sµg enhances hPSC self-renewal. Our study revealed that sµg enhanced the cell proliferation of hPSCs by regulating the expression of cell cycle-associated kinases. RNA-seq analysis indicated that in sµg condition the expression of differentiation and development pathways are downregulated, while multiple components of the ubiquitin proteasome system are upregulated, contributing to an enhanced self-renewal of hPSCs. These effects of sµg were not replicated in human fibroblasts. Taken together, our results highlight pathways and mechanisms in hPSCs vulnerable to microgravity that imposes significant impacts on human health and performance, physiology, and cellular and molecular processes.
目前仍缺乏对模拟微重力（sµg）对人类多能干细胞（hPSC）生物学效应的系统性研究。在此，我们使用快速旋转的二维回转器来研究sµg对hPSC增殖、自我更新和细胞周期调控的影响。我们观察到，与在1g条件下培养的细胞相比，在sµg条件下培养的hPSC中多能转录因子的蛋白质翻译显著上调。此外，端粒延长基因的表达也显著增加。分化实验表明，与1g条件下的细胞相比，在sµg条件下培养的hPSC对分化的敏感性较低。这些结果表明，sµg增强了hPSC的自我更新。我们的研究表明，sµg通过调节细胞周期相关激酶的表达来增强hPSC的细胞增殖。RNA测序分析表明，在sµg条件下，分化和发育途径的表达下调，而泛素蛋白酶体系统的多个成分上调，这有助于增强hPSC的自我更新。sµg的这些作用在人类成纤维细胞中并未重现。综上所述，我们的结果突出了hPSC中易受微重力影响的途径和机制，微重力对人类健康、性能、生理学以及细胞和分子过程具有重大影响。
