In the current study, we found that ectopic expression of hTERT not only blocked spontaneous differentiation and enhanced differentiation efficiency of hMSCs, but, what’s most fascinating, we successfully induced the extraordinary differentiation potential of hMSCs to germline and trophoectoderm lineages. We further demonstrated that hTERT might elicit phenomenon of dedifferentiation of hMSCs through epigenetic remodeling, especially DNA demethylation. A global CpG island methylation profile analysis revealed decreased methylation level of hTERT-transfected hMSCs and notably the demethylated genes were highly associated with development and differentiation genes which ensure the recapitulation of expression of these genes upon proper stimulation. Principal component analyses further indicated that the expression profile of the hTERT-transfected hMSCs converged toward ESCs. These data implicated great importance of the dedifferentiation effect of hTERT, which reversed pluripotency and blocked spontaneous differentiation of hMSCs through epigenetic mechanism and the current results take a great step forward in establishing the feasibility and applicability of adult stem cells in future clinical applications.
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