論文

査読有り
2017年11月

CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations

ELIFE
  • Hironobu Okuno
  • ,
  • Francois Renault Mihara
  • ,
  • Shigeki Ohta
  • ,
  • Kimiko Fukuda
  • ,
  • Kenji Kurosawa
  • ,
  • Wado Akamatsu
  • ,
  • Tsukasa Sanosaka
  • ,
  • Jun Kohyama
  • ,
  • Kanehiro Hayashi
  • ,
  • Kazunori Nakajima
  • ,
  • Takao Takahashi
  • ,
  • Joanna Wysocka
  • ,
  • Kenjiro Kosaki
  • ,
  • Hideyuki Okano

6
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.7554/eLife.21114
出版者・発行元
ELIFE SCIENCES PUBLICATIONS LTD

CHARGE syndrome is caused by heterozygous mutations in the chromatin remodeler, CHD7, and is characterized by a set of malformations that, on clinical grounds, were historically postulated to arise from defects in neural crest formation during embryogenesis. To better delineate neural crest defects in CHARGE syndrome, we generated induced pluripotent stem cells (iPSCs) from two patients with typical syndrome manifestations, and characterized neural crest cells differentiated in vitro from these iPSCs (iPSC-NCCs). We found that expression of genes associated with cell migration was altered in CHARGE iPSC-NCCs compared to control iPSC-NCCs. Consistently, CHARGE iPSC-NCCs showed defective delamination, migration and motility in vitro, and their transplantation in ovo revealed overall defective migratory activity in the chick embryo. These results support the historical inference that CHARGE syndrome patients exhibit defects in neural crest migration, and provide the first successful application of patient-derived iPSCs in modeling craniofacial disorders.

Web of Science ® 被引用回数 : 22

リンク情報
DOI
https://doi.org/10.7554/eLife.21114
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000416376900001&DestApp=WOS_CPL

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