Hippocampal single-nuclei RNA-sequencing identifies a role for Kdm5a in regulating cell identity

KDM5A is a chromatin remodeler disrupted in neurodevelopmental disease. To investigate the effect of losing KDM5A on the development of the hippocampus, we profiled hippocampi from wild type (WT) and Kdm5a -/- mice using single-nuclei RNA sequencing (snRNA-seq). We found that KDM5A regulates the development of specific subtypes of excitatory (CA1, CA2, CA3) and inhibitory (SST+, PVALB+) neurons, that loss of KDM5A leads to a more mature cellular identity in the hippocampus, and that KDM5A functions early in development to specify proper CA1 cell identity. Nuclei were isolated from hippocampal tissue of 20-week old WT and Kdm5a -/- (KO) mice and snRNA-seq data were generated by sequencing of 4 biological replicates per genotype using Illumina NovaSeq 6000.