RB maintains quiescence and prevents premature senescence through upregulation of DNMT1 in mesenchymal stromal cells.
Bottom Line: RB knockdown induces premature senescence and reduced differentiation potentials in early-passage MSCs.Furthermore, DNMT1 knockdown in early-passage MSCs induces senescence and reduces differentiation potentials, whereas DNMT1 overexpression in late-passage MSCs has the opposite effect.These results demonstrate that RB expressed in early-passage MSCs upregulates DNMT1 expression and inhibits senescence in MSCs.
Affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.Show MeSH
Related in: MedlinePlus
Mentions: To further confirm the roles of RB in maintaining stem cell properties and preventing senescence, we overexpressed RB in late-passage MSCs and evaluated its effects on proliferation, differentiation potentials, and senescence marker expression. Overexpression of RB in late-passage MSCs increased the proliferation rate (Figure 3A) and differentiation potentials (Figures 3B and 3C); decreased the expression of senescence-associated markers such as p21, p16 (Figure 3D), and APO-1 (Figure 3E); and reduced β-gal staining (Figure 3F). Similarly, RB overexpression via retroviral transduction in late-passage MSCs also increased the proliferation rate (Figure S3A), decreased the expression of p21 and p16 (Figure S3B), and reduced β-gal staining (Figure S3C). However, overexpression of RB in IMR90 fibroblasts decreased the proliferation rate (Figure S3D) and increased β-gal staining (Figure S3E), consistent with a previous report that showed RB’s role in replicative senescence of normal fibroblasts (Li et al., 1994). Together, these data suggest that RB plays an essential role in maintaining stem cell properties and prevents senescence in MSCs, but induces replicative senescence in fibroblasts.
Affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan, ROC.