TitleCellular Phenotypes in Human iPSC-Derived Neurons from a Genetic Model of Autism Spectrum Disorder.
Publication TypeJournal Article
Year of Publication2017
AuthorsDeshpande A, Yadav S, Dao DQ, Wu Z-Y, Hokanson KC, Cahill MK, Wiita AP, Jan Y-N, Ullian EM, Weiss LA
JournalCell Rep
Date Published2017 Dec 05
KeywordsAutism Spectrum Disorder, Autistic Disorder, Cell Differentiation, Chromosome Deletion, Chromosome Duplication, Chromosomes, Human, Pair 16, DNA Copy Number Variations, Humans, Induced Pluripotent Stem Cells, Megalencephaly, Microcephaly, Models, Genetic, Neurons

A deletion or duplication in the 16p11.2 region is associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. In addition to clinical characteristics, carriers of the 16p11.2 copy-number variant (CNV) manifest opposing neuroanatomical phenotypes-e.g., macrocephaly in deletion carriers (16pdel) and microcephaly in duplication carriers (16pdup). Using fibroblasts obtained from 16pdel and 16pdup carriers, we generated induced pluripotent stem cells (iPSCs) and differentiated them into neurons to identify causal cellular mechanisms underlying neurobiological phenotypes. Our study revealed increased soma size and dendrite length in 16pdel neurons and reduced neuronal size and dendrite length in 16pdup neurons. The functional properties of iPSC-derived neurons corroborated aspects of these contrasting morphological differences that may underlie brain size. Interestingly, both 16pdel and 16pdup neurons displayed reduced synaptic density, suggesting that distinct mechanisms may underlie brain size and neuronal connectivity at this locus.

Alternate JournalCell Rep
PubMed ID29212016
PubMed Central IDPMC5730067
Grant ListDP2 OD007449 / OD / NIH HHS / United States
K99 MH108648 / MH / NIMH NIH HHS / United States
R21 MH105745 / MH / NIMH NIH HHS / United States
T32 EY007120 / EY / NEI NIH HHS / United States