A synthetic small molecule for rapid induction of multiple pluripotency genes in mouse embryonic fibroblasts

作者：Pandian Ganesh N; Nakano Yusuke; Sato Shinsuke; Morinaga Hironobu; Bando Toshikazu; Nagase Hiroki; Sugiyama Hiroshi^*

来源：Scientific Reports, 2012, 2(1): 544.

DOI：10.1038/srep00544

Cellular reprogramming involves profound alterations in genome-wide gene expression that is precisely controlled by a hypothetical epigenetic code. Small molecules have been shown to artificially induce epigenetic modifications in a sequence independent manner. Recently, we showed that specific DNA binding hairpin pyrrole-imidazole polyamides (PIPs) could be conjugated with chromatin modifying histone deacetylase inhibitors like SAHA to epigenetically activate certain pluripotent genes in mouse fibroblasts. In our steadfast progress to improve the efficiency of SAHA-PIPs, we identified a novel compound termed, delta that could dramatically induce the endogenous expression of Oct-3/4 and Nanog. Genome-wide gene analysis suggests that in just 24 h and at nM concentration, delta induced multiple pluripotency-associated genes including Rex1 and Cdh1 by more than ten-fold. delta treated MEFs also rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching %26quot;ON%26apos;%26quot; the complex transcriptional gene network.

• 出版日期2012-7-30