Single-cell brain organoid screening identifies developmental defects in autism.

ABSTRACT: The development of the human brain involves unique processes (not observed in many other species) that can contribute to neurodevelopmental disorders^1-4. Cerebral organoids enable the study of neurodevelopmental disorders in a human context. We have developed the CRISPR-human organoids-single-cell RNA sequencing (CHOOSE) system, which uses verified pairs of guide RNAs, inducible CRISPR-Cas9-based genetic disruption and single-cell transcriptomics for pooled loss-of-function screening in mosaic organoids. Here we show that perturbation of 36 high-risk autism spectrum disorder genes related to transcriptional regulation uncovers their effects on cell fate determination. We find that dorsal intermediate progenitors, ventral progenitors and upper-layer excitatory neurons are among t

SUBMITTER: Li C 

PROVIDER: S-EPMC10499611 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature