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. Overall design: 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.

KDM5A是一种在神经发育疾病中发生功能紊乱的染色质重塑因子。为探究KDM5A缺失对海马发育的影响，本研究采用单细胞核RNA测序（single-nuclei RNA sequencing，snRNA-seq）技术，对野生型（wild type，WT）与Kdm5a基因敲除（Kdm5a -/-）小鼠的海马组织进行转录组谱分析。研究结果表明：KDM5A可调控特定亚型的兴奋性神经元（CA1、CA2、CA3区）与抑制性神经元（SST+、PVALB+）的发育；KDM5A缺失会导致海马细胞的细胞身份更趋成熟；且KDM5A在发育早期发挥功能，以确立正常的CA1细胞身份。整体实验设计：从20周龄的野生型与Kdm5a基因敲除（KO）小鼠的海马组织中分离细胞核，每个基因型设置4个生物学重复，通过Illumina NovaSeq 6000测序平台生成snRNA-seq数据。