Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen 52074, Germany; Institute for Biomedical Technology - Cell Biology, RWTH Aachen University Medical School, Aachen 52074, Germany; University of Southern Denmark, Functional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, Campusvej 55, Odense 5230, Denmark.
Helmholtz-Institute for Biomedical Engineering, Stem Cell Biology and Cellular Engineering, RWTH Aachen University Medical School, Aachen 52074, Germany; Institute for Biomedical Technology - Cell Biology, RWTH Aachen University Medical School, Aachen 52074, Germany.
Stem Cell Reports. 2020 Feb 11;14(2):201-209. doi: 10.1016/j.stemcr.2019.12.012. Epub 2020 Jan 23.
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 β-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.
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。目前尚不清楚细胞的代谢组在复制性衰老过程中如何变化，以及这种变化是否在不同的细胞类型中一致。我们直接比较了原代间充质基质细胞（MSCs）和诱导多能干细胞衍生的 MSCs（iMSCs）的培养扩增，直到它们达到生长停滞。两种细胞类型在形态、体外分化潜能、衰老相关β-半乳糖苷酶和 DNA 甲基化方面均发生了相似的变化。此外，MSCs 和 iMSCs 表现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中。随后，我们比较了 MSCs 和 iMSCs 的代谢组，观察到两种细胞类型中均存在重叠的衰老相关变化，包括烟酰胺核苷酸的下调和乳清酸的上调。综上所述，复制性衰老与高度可重复的衰老相关代谢组学表型相关，可用于监测细胞衰老状态。
