Dataset Information

TGF-? Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

ABSTRACT: It is generally thought that the proliferative capacity and differentiation potential of somatic stem cells, including mesenchymal stromal/stem cells (MSCs) and hematopoietic stem cells, decline with age. We investigated the effects of aging on human bone-derived MSCs expressing CD271 and SSEA-4 (double-positive MSCs [DPMSCs]). The percentages of DPMSCs in bone tissue decreased significantly with age. The DPMSCs from elderly patients (old DPMSCs) showed cellular senescence, which was evidenced by low growth potential, high senescence-associated ?-galactosidase activity, and elevated p16 and p21 CDK inhibitor levels. Moreover, old DPMSCs showed weak osteogenic differentiation potential and less hematopoiesis-supporting activity in comparison with young DPMSCs. Interestingly, the addition of transforming growth factor ?2 (TGF-?2) induced cellular senescence in young DPMSCs. With the exception of the adipogenic differentiation potential, all of the aging phenomena observed in old DPMSCs were reversed by the addition of anti-TGF-? antibodies. These results suggest that, in part, old DPMSCs accelerate cellular senescence through TGF-? signaling.

SUBMITTER: Kawamura H

PROVIDER: S-EPMC5918367 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

TGF-β Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

Kawamura Hiroshi H Nakatsuka Ryusuke R Matsuoka Yoshikazu Y Sumide Keisuke K Fujioka Tatsuya T Asano Hiroaki H Iida Hirokazu H Sonoda Yoshiaki Y

Stem cell reports 20180301 3

It is generally thought that the proliferative capacity and differentiation potential of somatic stem cells, including mesenchymal stromal/stem cells (MSCs) and hematopoietic stem cells, decline with age. We investigated the effects of aging on human bone-derived MSCs expressing CD271 and SSEA-4 (double-positive MSCs [DPMSCs]). The percentages of DPMSCs in bone tissue decreased significantly with age. The DPMSCs from elderly patients (old DPMSCs) showed cellular senescence, which was evidenced b ...[more]

PMID: 29478902

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Project description:Bone marrow mesenchymal stromal cells (BMSCs) are multipotent cells able to self-renew and differentiate, depending on the microenvironment, into adipocytes and osteoblasts. These cells have a limited number of replications and enter replicative senescence during in vitro expansion. The role of DNA methylation (DNAm) assumes importance in cell function and commitment; however, its exact contribution to BMSC differentiation and replicative senescence is still unclear. We performed a genome-wide DNAm analysis on BMSCs cultured in vitro at early passages and induced to differentiate into adipocytes and osteoblasts, and on replicative senescent BMSCs and HUVECs, to identify DNAm patterns of senescence and differentiation. We also compared BMSCs and HUVECs in replicative senescence and found that, in both cellular systems, genome-wide hypomethylation was accompanied by a higher-than-expected overlap of differentially methylated positions (DMPs) and concordance in terms of direction of the change. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on lineage-independent senescence-associated DMPs revealed 16 common pathways, including Insulin resistance, Molecule adhesion, and Wnt/β-catenin signaling. In both adipogenesis and osteogenesis, we observed a general demethylation of CpG sites compared with undifferentiated BMSCs with a higher number of DMPs in osteogenesis. KEGG analysis resulted in 30 pathways enriched in osteoblasts and only 2 in adipocytes when compared to undifferentiated cells. When comparing differentiated BMSCs with senescent ones, osteogenesis exhibited a greater overlap with senescence in terms of number of DMPs and direction of methylation change compared to adipogenesis. In conclusion, this study may be useful for future research on general mechanisms that occur in replicative senescence and furthermore to identify trajectories of BMSC differentiation and common aspects of differentiated and senescent cells.

Dataset Information

TGF-? Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

Publications

TGF-β Signaling Accelerates Senescence of Human Bone-Derived CD271 and SSEA-4 Double-Positive Mesenchymal Stromal Cells.

Similar Datasets

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