Human induced pluripotent stem cell derived neurons as a model for Williams-Beuren syndromeReport as inadecuate

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Molecular Brain

, 8:77

First Online: 24 November 2015Received: 11 September 2015Accepted: 13 November 2015


BackgroundWilliams-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.

ResultsWe 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.

ConclusionsOur findings provide insight into gene dysregulation and electrophysiological defects in WBS patient neurons.

KeywordsWilliams-Beuren Syndrome Human pluripotent stem cell Neural differentiation Transcriptome Disease modeling Ion channel AbbreviationsADHDAttention deficit, hyperactivity disorder

ECMExtracellular matrix

FDRFalse-discovery rate

iPSCInduced pluripotent stem cell

mEPSCminiature excitatory postsynaptic current

qRT-PCRquantitative reverse transcriptase real-time PCR

WBSWilliams-Beuren Syndrome



Shahryar Khattak, Elise Brimble and Wenbo Zhang contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s13041-015-0168-0 contains supplementary material, which is available to authorized users.

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Author: Shahryar Khattak - Elise Brimble - Wenbo Zhang - Kirill Zaslavsky - Emma Strong - P. Joel Ross - Jason Hendry - Seema Mit


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