Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells
| Autor: | Matteo Oliverio, Julia Franzen, Jonathan Hollmann, Alina Ostrowska, Jan-Wilhelm Kornfeld, Wolfgang Wagner, Roman Goetzke, Torsten Sieben, Björn Rath, Eduardo Fernandez-Rebollo |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Senescence Cell type induced pluripotent stem cells Biology Biochemistry Transcriptome 03 medical and health sciences replicative senescence transcriptomics 0302 clinical medicine Downregulation and upregulation Report Genetics Humans Induced pluripotent stem cell skin and connective tissue diseases lcsh:QH301-705.5 Cells Cultured Cellular Senescence Aged lcsh:R5-920 DNA methylation Gene Expression Profiling Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Middle Aged Phenotype metabolomics Cell biology 030104 developmental biology lcsh:Biology (General) Gene Expression Regulation Metabolome sense organs lcsh:Medicine (General) Energy Metabolism mesenchymal stromal cells Metabolic Networks and Pathways 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Fernandez-Rebollo, E, Franzen, J, Goetzke, R, Hollmann, J, Ostrowska, A, Oliverio, M, Sieben, T, Rath, B, Kornfeld, J-W & Wagner, W 2020, ' Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells ', Stem Cell Reports, vol. 14, no. 2, pp. 201-209 . https://doi.org/10.1016/j.stemcr.2019.12.012 Stem cell reports 14(2), 201-209 (2020). doi:10.1016/j.stemcr.2019.12.012 Stem Cell Reports Stem Cell Reports, Vol 14, Iss 2, Pp 201-209 (2020) |
| DOI: | 10.1016/j.stemcr.2019.12.012 |
| Popis: | Summary 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. Graphical Abstract Highlights • MSCs and iPSC-derived MSCs (iMSCs) acquired functional changes upon senescence • Senescence of MSCs and iMSCs evoked similar transcriptomic changes • Senescence of MSCs and iMSCs was associated with similar metabolomic phenotypes Wagner and colleagues show that expansion of iPSC-derived MSCs evokes molecular, functional, and metabolic changes similar to those observed in their primary counterparts. The highly consistent changes indicate that the metabolic phenotype can be used as a biomarker to assess the state of cellular aging, and this is relevant for regenerative medicine. |
| Databáze: | OpenAIRE |
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