Science (American Association for the Advancement of Science), 2020-11, Vol.370 (6520)
2020
Details
- Autor(en) / Beteiligte
- Titel
- In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes
- Ist Teil von
- Science (American Association for the Advancement of Science), 2020-11, Vol.370 (6520)
- Ort / Verlag
- United States: The American Association for the Advancement of Science
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.aaz6063Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7985844
- Format
- –
- Schlagworte
- Abnormalities, Animals, Ankyrins - genetics, Ankyrins - metabolism, Astrocytes, Autism, Autism Spectrum Disorders, Autistic Disorder - genetics, Autistic Disorder - pathology, Biological activity, Brain, Brain - abnormalities, Cerebral cortex, Correlation analysis, CRISPR, CRISPR-Cas Systems, Developmental Delays, Disorders, DNA-Binding Proteins - genetics, Effect Size, Embryos, Evaluation, Frameshift Mutation, Gene expression, Gene Expression Profiling, Gene sequencing, Genes, Genetic Loci, Genetic modification, Genetic screening, Genetics, Glial cells, Health risks, Humans, In vivo methods and tests, Loci, Mice, Microglia, Modularity, Modules, Mutation, Neocortex, Network analysis, Neurodevelopmental disorders, Neuroglia - metabolism, Neuroglia - pathology, Neuronal-glial interactions, Neurons, Neurons - metabolism, Neurons - pathology, Oligodendrocytes, Organoids, Perturbation, Phenotypes, Regression analysis, Regression models, Repressor Proteins - genetics, Ribonucleic acid, Risk, RNA, Screening Tests, Tissues, Transcription, Transcription Factors - genetics, Transcriptomics