A dynamic gene regulatory code drives synaptic development of hippocampal granule cells [snMO]

Connecting neurons into functional circuits requires the formation, maturation, and plasticity of synapses. While advances have been made in identifying individual genes regulating synapse development, the molecular programs orchestrating their action during circuit integration of neurons remain poorly understood. Here, we have employed a combination of single nuclei transcriptome and epigenome sequencing (single nuclei multiome) to study the development of the hippocampus. The hippocampus contains several excitatory and inhibitory cell types, as well as astrocytes, glia and other immune cells of the brain. The hipocampal trisynaptic circuit (DG-CA3-CA1) is essential for learning and memory. This study provides single-cell multiome data of hippocampal postnatal (P) development (P5, P10, P15, and P28), offering an in-depth analysis of gene regulatory networks during granule cell synapse formation. Together, these findings highlight the networks of key TFs and target genes orchestrating GC synapse development. Hippocampi from C57Bl6 mice were homogenized, nuclei were isolated and processed for both RNA sequencing and ATAC sequencing. This process was repeated using hippocampi from mice at postnatal day (P)5, P10, P15 and P28.