In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes

Author:

Jin Xin1234ORCID,Simmons Sean K.356,Guo Amy3,Shetty Ashwin S.235ORCID,Ko Michelle2,Nguyen Lan36,Jokhi Vahbiz2,Robinson Elise357,Oyler Paul2ORCID,Curry Nathan2,Deangeli Giulio2,Lodato Simona8ORCID,Levin Joshua Z.356ORCID,Regev Aviv36910ORCID,Zhang Feng3410ORCID,Arlotta Paola235ORCID

Affiliation:

1. Society of Fellows, Harvard University, Cambridge, MA, USA.

2. Department of Stem Cell and Regenerative Biology, Harvard University, MA, USA.

3. Broad Institute of MIT and Harvard, Cambridge, MA, USA.

4. McGovern Institute of Brain Science, Department of Brain and Cognitive Science, Department of Biological Engineering, Massachussetts Institute of Technology (MIT), Cambridge, MA, USA.

5. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

6. Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

7. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

8. Department of Biomedical Sciences and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Clinical and Research Center, Humanitas University, Milan, Italy.

9. Koch Institute of Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA, USA.

10. Howard Hughes Medical Institute, Chevy Chase, MD, USA.

Abstract

An in vivo analysis of autism risk genes CRISPR targeting in vivo, especially in mammals, can be difficult and time consuming when attempting to determine the effects of a single gene. However, such studies may be required to identify pathological gene variants with effects in specific cells along a developmental trajectory. To study the function of genes implicated in autism spectrum disorders (ASDs), Jin et al. applied a gene-editing and single-cell–sequencing system, Perturb-Seq, to knock out 35 ASD candidate genes in multiple mice embryos (see the Perspective by Treutlein and Camp). This method identified networks of gene expression in neuronal and glial cells that suggest new functions in ASD-related genes. Science , this issue p. eaaz6063 ; see also p. 1038

Funder

National Institutes of Health

Howard Hughes Medical Institute

National Human Genome Research Institute

Brain and Behavior Research Foundation

Stanley Center for Psychiatric Research, Broad Institute

Klarman Cell Observatory, Broad Institute

Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT

New York Stem Cell Foundation

G. Harold and Leila Y. Mathers Foundation

Poitras Center for Affective Disorders Research at MIT

Harvard William F. Milton Grant

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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