In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes.
Science
; 370(6520)2020 11 27.
Article
in En
| MEDLINE
| ID: mdl-33243861
ABSTRACT
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 RNA-sequencing 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autistic Disorder
/
Brain
/
Neuroglia
/
Neurons
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Science
Year:
2020
Document type:
Article