Research Abstract


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

2012年7月30日 Scientific Reports 2 : 544 doi: 10.1038/srep00544


Ganesh N. Pandian1, 仲野 祐輔2, 佐藤 慎祐1, 森永 浩伸2, 板東 俊和2, 永瀬 浩喜3,4 & 杉山 弘1,2

  1. 京都大学物質-細胞統合システム拠点(WPI-iCeMS)
  2. 京都大学大学院 理学研究科 化学専攻
  3. 日本大学医学部 癌遺伝学分野
  4. 千葉県がんセンター研究所
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, δ 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, δ induced multiple pluripotency-associated genes including Rex1 and Cdh1 by more than ten-fold. δ treated MEFs also rapidly overcame the rate-limiting step of epithelial transition in cellular reprogramming by switching “ ” the complex transcriptional gene network.