Ephrin-B2 deletion in GABAergic neurons induces cognitive deficits associated with single-nucleus transcriptomic differences in the prefrontal cortex by Peijun Ju & Yu Fang & Siying Xiang & Weidi Wang & Ying Sun & Wei Wang & Yanli Ding & Chao Luo & Ping Jiang & Jianhua Chen instant download

Ephrin-B2 deletion in GABAergic neurons induces cognitive deficits associated with single-nucleus transcriptomic differences in the prefrontal cortex by Peijun Ju & Yu Fang & Siying Xiang & Weidi Wang & Ying Sun & Wei Wang & Yanli Ding & Chao Luo & Ping Jiang & Jianhua Chen instant download

BMC Biology,AbstractBackground Ephrin-B2 (EB2) signaling plays a crucial role in regulating memory and synaptic plasticity. Comprehensive identifcation of cell-type-specifc transcriptomic changes in EB2 knockout mice is expected to shed light on potential mechanisms associated with EB2 signaling in cognitive functions.Results Our study captures changes in cell populations in response to EB2 manipulation and reveals previously uncharacterized cell types (CPA6+inhibitory neurons) in the mPFC. We validated the diferential transcriptomic activity of Pbx1 and Meis1 in CPA6+neurons using fuorescence in situ hybridization (ISH) in EB2-vGATCre mice. The aberrant presence of CPA6+neurons in the mPFC may correlate with cognitive impairments induced by EB2 deletion in vGAT+neurons. Analyzing diferentially expressed genes (DEGs) in individual cell clusters, we identifed alterations related to synapse organization and development, cognition, amyloid-beta formation, and locomotor behavior. Additionally, our DEGs overlapped with human genome-wide association study (GWAS) candidate genes related to cognition and anxiety, underscoring the relevance of our mouse model to human disease.Conclusions We present a comprehensive atlas of cell-type-specifc gene expression changes in this synaptic defciency model and identify novel cell-type-specifc targets implicated in cognitive defcits. Our investigation provides a detailed map of the cell types, genes, and pathways altered in this inhibitory synaptic defciency model.Keywords Ephrin-B2, Cognition, Single-nucleus RNA sequencing, GABAergic neurons