A scalable, high-throughput neural development platform identifies shared impact of ASD genes on cell fate and differentiation.

ABSTRACT:

Background

Deleterious mutations in hundreds of genes confer high risk for neurodevelopmental disorders (NDDs), posing significant challenges for therapeutic development. Identifying convergent pathways shared across NDD genes could reveal high-impact therapeutic targets.

Methods

To identity convergent pathways in NDD genes, we optimized Perturb-seq, a method combining CRISPR perturbation with single-cell RNA sequencing (scRNA-seq), and applied structural topic modeling (STM) to simultaneously assess impact on cell fate and developmental stage. We then studied a subset of autism spectrum disorder (ASD) genes implicated in regulation of gene expression using these improved molecular and analytical approaches.

Results

Results from targeting 60 high-confidence ASD risk g

SUBMITTER: Wang X 

PROVIDER: S-EPMC11463611 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature