Institute of Cell and Development Biology, College of Life Sciences, Zhejiang University, Hangzhou, China.
Departments of Cell Biology and Otolaryngology, Emory University School of Medicine, Atlanta, Georgia.
Cell Prolif. 2019 Mar;52(2):e12539. doi: 10.1111/cpr.12539. Epub 2018 Nov 5.
Exposure to microgravity induces many adaptive and pathological changes in human bone marrow mesenchymal stem cells (hBMSCs). However, the underlying mechanisms of these changes are poorly understood. We revealed the gene expression patterns of hBMSCs under normal ground (NG) and simulated microgravity (SMG), which showed an interpretation for these changes by gene regulation and signal pathways analysis.
In this study, hBMSCs were osteogenically induced for 0, 2, 7 and 14 days under normal ground gravity and simulated microgravity, followed by analysis of the differences in transcriptome expression during osteogenic differentiation by RNA sequencing and some experimental verification for these results.
The results indicated that 837, 399 and 894 differentially expressed genes (DEGs) were identified in 2, 7 and 14 days samples, respectively, out of which 13 genes were selected for qRT-PCR analysis to confirm the RNA-sequencing results. After analysis, we found that proliferation was inhibited in the early stage of induction. In the middle stage, osteogenic differentiation was inhibited, whereas adipogenic differentiation benefited from SMG. Moreover, SMG resulted in the up-regulation of genes specific for tumorigenesis in the later stage.
Our data revealed that SMG inhibits the proliferation and inhibits the differentiation towards osteoblasts but promotes adipogenesis. SMG also selects highly tumorigenic cells for survival under prolonged SMG.
微重力暴露会引起人骨髓间充质干细胞（hBMSCs）的许多适应性和病理性变化。然而，这些变化的潜在机制尚未完全了解。我们揭示了 hBMSCs 在正常地面（NG）和模拟微重力（SMG）下的基因表达模式，通过基因调控和信号通路分析对这些变化进行了解释。
在这项研究中，hBMSCs 在正常地面重力和模拟微重力下进行成骨诱导 0、2、7 和 14 天，然后通过 RNA 测序分析成骨分化过程中转录组表达的差异，并对这些结果进行了一些实验验证。
结果表明，在 2、7 和 14 天的样本中分别鉴定出 837、399 和 894 个差异表达基因（DEGs），其中 13 个基因被选择进行 qRT-PCR 分析以验证 RNA-seq 结果。分析后发现，诱导早期增殖受到抑制。在中期，成骨分化受到抑制，而脂肪生成则受益于 SMG。此外，SMG 导致后期与肿瘤发生相关的基因上调。
我们的数据表明，SMG 抑制增殖并抑制向成骨细胞分化，但促进脂肪生成。SMG 还在长时间的 SMG 下选择具有高致瘤性的细胞存活。
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