BackgroundMesenchymal stem cells (MSCs) hold great promise for the treatment of difficult diseases. As MSCs represent a rare cell population, ex vivo expansion of MSCs is indispensable to obtain sufficient amounts of cells for therapies and tissue engineering. However, spontaneous differentiation and aging of MSCs occur during expansion and the molecular mechanisms involved have been poorly understood.Methodology/Principal FindingsHuman MSCs in early and late passages were examined for their expression of genes involved in osteogenesis to determine their spontaneous differentiation towards osteoblasts in vitro, and of genes involved in self-renewal and proliferation for multipotent differentiation potential. In parallel, promoter DNA methylation and hostone H3 acetylation levels were determined. We found that MSCs underwent aging and spontaneous osteogenic differentiation upon regular culture expansion, with progressive downregulation of TERT and upregulation of osteogenic genes such as Runx2 and ALP. Meanwhile, the expression of genes associated with stem cell self-renewal such as Oct4 and Sox2 declined markedly. Notably, the altered expression of these genes were closely associated with epigenetic dysregulation of histone H3 acetylation in K9 and K14, but not with methylation of CpG islands in the promoter regions of most of these genes. bFGF promoted MSC proliferation and suppressed its spontaneous osteogenic differentiation, with corresponding changes in histone H3 acetylation in TERT, Oct4, Sox2, Runx2 and ALP genes.Conclusions/SignificanceOur results indicate that histone H3 acetylation, which can be modulated by extrinsic signals, plays a key role in regulating MSC aging and differentiation.
Transformations of alkene and alkyne substrates relevant to p-Lewis acid catalysis have been performed using low-valent Ga(I) species for the first time. [Ga(I)(PhF) 2 ] + [Al(OR F ) 4 ] À and gallium dichloride (i. e. [Ga(I)] + [GaCl 4 ] À ) proved to be efficient catalysts for cycloisomerizations, Friedel-Crafts reactions, transfer hydrogenations, and reductive hydroarylations. Their activity is compared to more common Ga(III) complexes. This study shows that even the readily available and yet overlooked gallium dichloride salt can be a more active p-Lewis acid catalyst than gallium trichloride or other Ga(III) species.
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