Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells
Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells
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DOI：
10.1016/j.stemcr.2019.12.012
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发表时间：
2020-02-11
影响因子：
5.9
通讯作者：
Wagner, Wolfgang
中科院分区：
文献类型：
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作者：
Fernandez-Rebollo, Eduardo;Franzen, Julia;Wagner, Wolfgang
原代细胞的长期培养以功能和分泌变化为特征，最终导致复制性衰老。在很大程度上还不清楚细胞的代谢体在复制衰老过程中是如何变化的，以及这种变化在不同类型的细胞中是否一致。我们直接比较了原代间充质干细胞(MSCs)和诱导多能干细胞来源的MSCs(IMSCs)的培养扩增，直到它们达到生长停滞。这两种类型的细胞在形态、体外分化潜能、衰老相关的β-半乳糖苷酶和DNA甲基化方面获得了相似的变化。此外，MSCs和iMSCs显示出重叠的基因表达变化，特别是在与代谢过程相关的功能类别。随后，我们比较了MSCs和iMSCs的代谢物，观察到两种细胞类型与衰老相关的重叠变化，包括烟酰胺核苷酸下调和奥罗里酸上调。综上所述，复制性衰老与高度可重复性的衰老相关代谢组学表型有关，该表型可用于监测细胞衰老状态。
Long-term culture of primary cells is characterized by functional and secretory changes, which ultimately result in replicative senescence. It is largely unclear how the metabolome of cells changes during replicative senescence and if such changes are consistent across different cell types. We have directly compared culture expansion of primary mesenchymal stromal cells (MSCs) and induced pluripotent stem cell-derived MSCs (iMSCs) until they reached growth arrest. Both cell types acquired similar changes in morphology, in vitro differentiation potential, senescence-associated beta-galactosidase, and DNA methylation. Furthermore, MSCs and iMSCs revealed overlapping gene expression changes, particularly in functional categories related to metabolic processes. We subsequently compared the metabolomes of MSCs and iMSCs and observed overlapping senescence-associated changes in both cell types, including downregulation of nicotinamide ribonucleotide and upregulation of orotic acid. Taken together, replicative senescence is associated with a highly reproducible senescence-associated metabolomics phenotype, which may be used to monitor the state of cellular aging.