Telomere Rejuvenation & Maintenance in Chemical Reprogramming for Pluripotency

The Rejuvenation of Telomeres during Chemical Induction in Pluripotent stem cells

CiPSCs (chemically induced pluripotent cells) could be an attractive alternative for stem cell therapy. Telomere lengths must be sufficient for pluripotent cells to self-renew and remain genomically stable. The mechanisms and dynamics of telomere reprograming in CiPSCs are still a mystery. After clonal formation, we show that CiPSCs can acquire telomere elongation with increasing passages. Telomere lengthening is a result of both telomerase and recombination mechanisms. Telomere lengths are a strong indicator of the degree of reprogramming and pluripotency of CiPSCs. Telomere shortening and damage occur late in the lengthy induction process, which limits CiPSC generation. We found that histone-crotonylation caused by crotonic acids can activate genes in two cells, such as Zscan4, maintain telomeres and promote CiPSC formation. Crotonylation reduces the amount of heterochromatic HP1a and H3K9me3 at subtelomeres, and Zscan4 loci. Together, telomere renewal is linked to reprogramming of CiPSCs and their pluripotency. Crotonylation enhances telomere maintenance, and chemically-induced reprogramming of CiPSCs to pluripotency.


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