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In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes
Name
nihms-1666890.pdf
Description
Accepted version
Size
2.8 MB
Format
Adobe PDF
Checksum (MD5)
377d1996f387deb58713b6711b02ede9
Author(s)
Jin, Xin
Simmons, Sean K
Guo, Amy
Shetty, Ashwin S
Ko, Michelle
Nguyen, Lan
Jokhi, Vahbiz
Robinson, Elise
Oyler, Paul
Curry, Nathan
Date Issued
2020
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Version
Author's final manuscript
Abstract
© 2020 American Association for the Advancement of Science. All rights reserved. The number of disease risk genes and loci identified through human genetic studies far outstrips the capacity to systematically study their functions. We applied a scalable genetic screening approach, in vivo Perturb-Seq, to functionally evaluate 35 autism spectrum disorder/neurodevelopmental delay (ASD/ND) de novo loss-of-function risk genes. Using CRISPR-Cas9, we introduced frameshift mutations in these risk genes in pools, within the developing mouse brain in utero, followed by single-cell RNAsequencing of perturbed cells in the postnatal brain. We identified cell type-specific and evolutionarily conserved gene modules from both neuronal and glial cell classes. Recurrent gene modules and cell types are affected across this cohort of perturbations, representing key cellular effects across sets of ASD/ND risk genes. In vivo Perturb-Seq allows us to investigate how diverse mutations affect cell types and states in the developing organism.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
10.1126/science.aaz6063
