Enhanced self-renewal of human pluripotent stem cells by simulated microgravity
Abstract 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 sig...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | npj Microgravity |
| Online Access: | https://doi.org/10.1038/s41526-022-00209-4 |
| _version_ | 1797642379276058624 |
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| author | S. Timilsina T. Kirsch-Mangu S. Werth B. Shepard T. Ma L. G. Villa-Diaz |
| author_facet | S. Timilsina T. Kirsch-Mangu S. Werth B. Shepard T. Ma L. G. Villa-Diaz |
| author_sort | S. Timilsina |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T13:59:14Z |
| format | Article |
| id | doaj.art-818bc053d531497691cc52bb231b8a4a |
| institution | Directory Open Access Journal |
| issn | 2373-8065 |
| language | English |
| last_indexed | 2024-03-11T13:59:14Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Microgravity |
| spelling | doaj.art-818bc053d531497691cc52bb231b8a4a2023-11-02T05:13:28ZengNature Portfolionpj Microgravity2373-80652022-07-01811910.1038/s41526-022-00209-4Enhanced self-renewal of human pluripotent stem cells by simulated microgravityS. Timilsina0T. Kirsch-Mangu1S. Werth2B. Shepard3T. Ma4L. G. Villa-Diaz5Department of Biological Sciences, Oakland UniversityDepartment of Biological Sciences, Oakland UniversityDepartment of Biological Sciences, Oakland UniversityDepartment of Biological Sciences, Oakland UniversityDepartment of Computer Science, Engineering, Oakland UniversityDepartment of Biological Sciences, Oakland UniversityAbstract 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.https://doi.org/10.1038/s41526-022-00209-4 |
| spellingShingle | S. Timilsina T. Kirsch-Mangu S. Werth B. Shepard T. Ma L. G. Villa-Diaz Enhanced self-renewal of human pluripotent stem cells by simulated microgravity npj Microgravity |
| title | Enhanced self-renewal of human pluripotent stem cells by simulated microgravity |
| title_full | Enhanced self-renewal of human pluripotent stem cells by simulated microgravity |
| title_fullStr | Enhanced self-renewal of human pluripotent stem cells by simulated microgravity |
| title_full_unstemmed | Enhanced self-renewal of human pluripotent stem cells by simulated microgravity |
| title_short | Enhanced self-renewal of human pluripotent stem cells by simulated microgravity |
| title_sort | enhanced self renewal of human pluripotent stem cells by simulated microgravity |
| url | https://doi.org/10.1038/s41526-022-00209-4 |
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