Microdeletions and microduplications of the 16p11.2 chromosomal locus are associated with syndromic neurodevelopmental disorders and reciprocal physiological conditions such as macro/microcephaly and high/low body mass index. To facilitate cellular and molecular investigations into these phenotypes, 65 clones of human induced pluripotent stem cells (hiPSCs) were generated from 13 individuals with 16p11.2 copy number variations (CNVs). To ensure these cell lines were suitable for downstream mechanistic investigations, a customizable bioinformatic strategy for the detection of random integration and expression of reprogramming vectors was developed and leveraged towards identifying a subset of 'footprint'-free hiPSC clones. Transcriptomic profiling of cortical neural progenitor cells derived from these hiPSCs identified alterations in gene expression patterns which precede morphological abnormalities reported at later neurodevelopmental stages. Interpreting clinical information—available with the cell lines by request from the Simons Foundation Autism Research Initiative—with this transcriptional data revealed disruptions in gene programs related to both nervous system function and cellular metabolism. As demonstrated by these analyses, this publicly available resource has the potential to serve as a powerful medium for probing the etiology of developmental disorders associated with 16p11.2 CNVs.
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Julien G Roth
Department of Neurosurgery and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States
Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
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The authors declare that no competing interests exist.
Aditya Asokan
Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
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The authors declare that no competing interests exist.
Victoria M Mallett
Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
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Hui Gai
Department of Neurosurgery and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States
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Yogendra Verma
Department of Neurosurgery and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States
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Stephen Weber
Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
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Carol Charlton
Department of Neurosurgery, Stanford University School of Medicine, Stanford, United States
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Jonas L Fowler
Department of Neurosurgery and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States
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The authors declare that no competing interests exist.
Kyle M Loh
Department of Neurosurgery and The Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United States
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The authors declare that no competing interests exist.
Ricardo E Dolmetsch
Department of Neurobiology, Stanford University School of Medicine, Stanford, United States
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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