title: Human induced pluripotent stem cell derived neurons as a model for Williams-Beuren syndrome.
abstract: BACKGROUND
  Williams-Beuren Syndrome (WBS) is caused by the microdeletion of approximately 25 genes on chromosome 7q11.23, and is characterized by a spectrum of cognitive and behavioural features.
  
  
  RESULTS
  We generated cortical neurons from a WBS individual and unaffected (WT) control by directed differentiation of induced pluripotent stem cells (iPSCs). Single cell mRNA analyses and immunostaining demonstrated very efficient production of differentiated cells expressing markers of mature neurons of mixed subtypes and from multiple cortical layers. We found that there was a profound alteration in action potentials, with significantly prolonged WBS repolarization times and a WBS deficit in voltage-activated K(+) currents. Miniature excitatory synaptic currents were normal, indicating that unitary excitatory synaptic transmission was not altered. Gene expression profiling identified 136 negatively enriched gene sets in WBS compared to WT neurons including gene sets involved in neurotransmitter receptor activity, synaptic assembly, and potassium channel complexes.
  
  
  CONCLUSIONS
  Our findings provide insight into gene dysregulation and electrophysiological defects in WBS patient neurons.
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. shahryar.khattak@crt-dresden.de.
authors.forename: Shahryar
authors.initials: S
authors.lastname: Khattak
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. ebrimble@bu.edu.
authors.forename: Elise
authors.initials: E
authors.lastname: Brimble
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON, Canada. wenbo.zhang@utoronto.ca.|Department of Physiology, University of Toronto, Toronto, ON, Canada. wenbo.zhang@utoronto.ca.|University of Toronto Centre for the Study of Pain, University of Toronto, Toronto, ON, Canada. wenbo.zhang@utoronto.ca.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. kirill.zaslavsky@mail.utoronto.ca.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. kirill.zaslavsky@mail.utoronto.ca.
authors.forename: Kirill
authors.initials: K
authors.lastname: Zaslavsky
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. emma.strong@mail.utoronto.ca.
authors.forename: Emma
authors.initials: E
authors.lastname: Strong
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. pjoelross@gmail.com.
authors.forename: P Joel
authors.initials: PJ
authors.lastname: Ross
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. jason.hendry@mail.utoronto.ca.
authors.forename: Jason
authors.initials: J
authors.lastname: Hendry
authors.affiliation: Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada. seema.mital@Sickkids.ca.
authors.forename: Seema
authors.initials: S
authors.lastname: Mital
authors.affiliation: Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, ON, Canada. michael.salter@Sickkids.ca.|Department of Physiology, University of Toronto, Toronto, ON, Canada. michael.salter@Sickkids.ca.|University of Toronto Centre for the Study of Pain, University of Toronto, Toronto, ON, Canada. michael.salter@Sickkids.ca.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Salter
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. lucy.osborne@utoronto.ca.|Institute of Medical Science, University of Toronto, Toronto, ON, Canada. lucy.osborne@utoronto.ca.|Department of Medicine, University of Toronto, Toronto, ON, Canada. lucy.osborne@utoronto.ca.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Osborne
authors.affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, ON, Canada. jellis@sickkids.ca.|Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada. jellis@sickkids.ca.|Developmental and Stem Cell Biology, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning, 686 Bay St, 16th Floor - Room 9705, Toronto, ON, M5G 0A4, Canada. jellis@sickkids.ca.
authors.forename: James
authors.initials: J
authors.lastname: Ellis
mesh_terms: D000200:Action Potentials; D002454:Cell Differentiation; D048430:Cell Shape; D015536:Down-Regulation; D020869:Gene Expression Profiling; D057898:Hemizygote; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008954:Models, Biological; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D015221:Potassium Channels / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D018980:Williams Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015221:Potassium Channels