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

Elife. 2017 Nov 28:6:e21114. doi: 10.7554/eLife.21114.


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.

Keywords: CHARGE syndrome; CHD7; cell migration; developmental biology; disease modeling; human; human biology; induced pluripotent stem cells; medicine; neural crest; stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHARGE Syndrome / genetics
  • CHARGE Syndrome / physiopathology*
  • Cell Differentiation
  • Cell Movement*
  • Cells, Cultured
  • Chick Embryo
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics
  • Gene Expression Profiling
  • Humans
  • Induced Pluripotent Stem Cells / physiology
  • Mutant Proteins / genetics
  • Mutation
  • Neural Crest / physiology*


  • DNA-Binding Proteins
  • Mutant Proteins
  • DNA Helicases
  • CHD7 protein, human

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.