“The field has been limited by the sheer time and effort that it takes to make one model at a time to test the function of single genes. Now, we have shown the potential of studying gene function in a developing organism in a scalable way, which is an exciting first step to understanding the mechanisms that lead to autism spectrum disorder and other complex psychiatric conditions, and to eventually develop treatments for these devastating conditions,” said Arlotta, who is also an institute member of the Broad Institute and part of the Broad’s Stanley Center for Psychiatric Research. “Our work also paves the way for Perturb-Seq to be applied to organs beyond the brain, to enable scientists to better understand the development or function of different tissue types, as well as pathological conditions.”

“Through genome sequencing efforts, a very large number of genes have been identified that, when mutated, are associated with human diseases. Traditionally, understanding the role of these genes would involve in-depth studies of each gene individually. By developing Perturb-seq for in vivo applications, we can start to screen all of these genes in animal models in a much more efficient manner, enabling us to understand mechanistically how mutations in these genes can lead to disease,” said Zhang, who is also the James and Patricia Poitras Professor of Neuroscience at MIT and a professor of brain and cognitive sciences and biological engineering at MIT.

This research was supported by the Stanley Center for Psychiatric Research at the Broad Institute, the National Institutes of Health, the Brain and Behavior Research Foundation’s NARSAD Young Investigator Grant, Harvard University’s William F. Milton Fund, the Klarman Cell Observatory, the Howard Hughes Medical Institute, a Center for Cell Circuits grant from the National Human Genome Research Institute’s Centers of Excellence in Genomic Science, the New York Stem Cell Foundation, the Mathers Foundation, the Poitras Center for Affective Disorders Research at MIT, the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT, and J. and P. Poitras.