Single-nucleus RNA-seq atlas of 17 ASD-risk mouse lines under early-postnatal fluoxetine or lithium exposure (4-plex On-Chip Multiplexed)

Autism spectrum disorder (ASD) involves more than 1,000 risk genes, complicating mechanistic subtyping. To resolve the cellular basis of transcriptomic stratification, we generated single-nucleus RNA-seq (snRNA-seq) profiles from the prefrontal cortex of 17 mouse lines carrying ASD-associated synaptic, chromatin-regulatory, and signaling mutations, together with C57BL/6J wild-type controls. Both sexes were profiled under baseline and early-postnatal (P3-P25) fluoxetine or lithium exposure. Four mice were multiplexed per 10x Genomics GEM-X v4 4-plex On-Chip Multiplexing (OCM) library, yielding 53 sequencing libraries (tubes) covering 212 individual mice. After downstream QC, approximately 1,016,895 nuclei from 205 mice were retained at postnatal day 25.