4.5 Article

Enhanced self-renewal of human pluripotent stem cells by simulated microgravity

Journal

NPJ MICROGRAVITY
Volume 8, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41526-022-00209-4

Keywords

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Funding

  1. Michigan Space Grant Consortium, Oakland University REF funding
  2. NSF [2026049]
  3. Direct For Biological Sciences
  4. Div Of Molecular and Cellular Bioscience [2026049] Funding Source: National Science Foundation

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This study investigated the effects of simulated microgravity on human pluripotent stem cells. The results showed that microgravity enhanced cell proliferation and self-renewal, while affecting cell differentiation and cell cycle regulation. These findings are important for understanding the impacts of microgravity on human health and physiological processes.
A systematic study on the biological effects of simulated microgravity (s mu g) on human pluripotent stem cells (hPSC) is still lacking. Here, we used a fast-rotating 2-D clinostat to investigate the s mu g 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 s mu g compared to cells cultured in lg conditions. In addition to a significant increase in expression of telomere elongation genes. Differentiation experiments showed that hPSC cultured in spy condition were less susceptible to differentiation compared to cells in 1g conditions. These results suggest that s mu g enhances hPSC self-renewal. Our study revealed that s mu g enhanced the cell proliferation of hPSCs by regulating the expression of cell cycle-associated kinases. RNA-seq analysis indicated that in s mu g 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 s mu g 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.

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