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Stem Cell Reports. 2020 Feb 11;14(2):201-209. doi: 10.1016/j.stemcr.2019.12.012. Epub 2020 Jan 23.

Senescence-Associated Metabolomic Phenotype in Primary and iPSC-Derived Mesenchymal Stromal Cells.

Author information

1
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. Electronic address: ef-r@bmb.sdu.dk.
2
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.
3
Max Planck Institute for Metabolism Research (MPI-MR), Noncoding RNAs and Energy Homeostasis, Gleueler Strasse 50, Cologne 50931, Germany; Cologne Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne 50931, Germany.
4
Department for Orthopedics, RWTH Aachen University Medical School, Aachen 52074, Germany.
5
Max Planck Institute for Metabolism Research (MPI-MR), Noncoding RNAs and Energy Homeostasis, Gleueler Strasse 50, Cologne 50931, Germany; Cologne Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne 50931, Germany; University of Southern Denmark, Functional Genomics and Metabolism Unit, Department for Biochemistry and Molecular Biology, Campusvej 55, Odense 5230, Denmark.
6
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. Electronic address: wwagner@ukaachen.de.

Abstract

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.

KEYWORDS:

DNA methylation; induced pluripotent stem cells; mesenchymal stromal cells; metabolomics; replicative senescence; transcriptomics

PMID:
31983656
PMCID:
PMC7013233
DOI:
10.1016/j.stemcr.2019.12.012

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