Conversion from senescent cells to pluripotent cells by modulating expression of Alu retroelements.

摘要

Epigenetic chromatin regulations in aging have been intensely studied. During aging, overall DNA methylation tends to decrease, although some loci are specifically methylated. Histone modifications across the genome are also known to be modulated during aging. For instance, the globular accumulation of heterochromatin associated with methylation of histone H3 at lysine 9 and heterochromatin protein HP1, referred to as senescence-associated heterochromatic foci (SAHFs), was observed in senescent human fibroblasts. However, the exact roles of epigenetic chromatin regulations in cellular senescence remain elusive. As an additional layer of complexity, DNA damage is known to be accumulated during aging.It was previously shown that DNA damage induced by chemical treatments can derepress SINE (short interspersed element) retrotrans-posons, such as Alu, in human cells. Wang et al. set out to test the possibility that DNA damage during aging causes derepression of the Alu retroelements.The authors employed the ex vivo aging system with human adult adipose-derived mesenchymal stem cells (hADSCs), and found that Alu expression is dramatically increased in senescent cells with formation of gammaH2AX (phosphorylated histone variant H2AX) nuclear foci.