Reprogramming Suppresses Premature Senescence Phenotypes of Werner Syndrome Cells and Maintains Chromosomal Stability over Long-Term Culture

• DOI: 10.1371/journal.pone.0112900
• Publication Date: 2014-11-12T19:19:42Z
• Authors: Akira Shimamoto; Harunobu Kagawa; Kazumasa Zensho; Yukihiro Sera; Yasuhiro Kazuki; Mitsuhiko Osaki; Mitsuo Oshimura; Yasuhito Ishigaki; Kanya Hamasaki; Yoshiaki Kodama; Shinsuke Yuasa; Keiichi Fukuda; Kyotaro Hirashima; Hiroyuki Seimiya; Hirofumi Koyama; Takahiko Shimizu; Minoru Takemoto; Koutaro Yokote; Makoto Goto; Hidetoshi Tahara
• Keywords: Reprogramming; Chromosome instability; Senescence; Premature aging; Werner syndrome; Progeria

Werner syndrome (WS) is a premature aging disorder characterized by chromosomal instability and cancer predisposition. Mutations in WRN are responsible for the disease cause telomere dysfunction, resulting accelerated aging. Recent studies have revealed that cells from WS patients can be successfully reprogrammed into induced pluripotent stem (iPSCs). In present study, we describe effects of long-term culture on iPSCs, which acquired maintained infinite proliferative potential self-renewal over 2 years. After cultures, iPSCs exhibited stable undifferentiated states differentiation capacity, upregulation senescence-associated genes was completely suppressed despite deficiency. also showed recapitulation phenotypes during differentiation. Furthermore, karyotype analysis indicated were stable, half descendant clones had profiles similar to those parental cells. These unexpected properties might achieved expression endogenous telomerase gene reprogramming, trigger reactivation leading suppression both replicative senescence dysfunction findings demonstrated reprogramming could lead stability long term. will provide opportunities identify affected lineages develop new strategy treatment WS.