{"id":"doi:10.1016/j.gendis.2025.101969","kind":"article","title":"Spatial transcriptomics revealed the regulatory role of CCN1 to microglia distribution through region-specific cellular interactions","authors":["Bai Z","Chang Z","Wang S","Zheng J","Wu H","Liu H","Zhang Y","Xie J","Bai Q","Yin J","Wu Y","Shen Q","Gao S","Gao Y"],"author_count":14,"year":2026,"published":"2025-12-09","venue":"Genes & diseases","cited_by":0,"doi":"10.1016/j.gendis.2025.101969","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.gendis.2025.101969","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.gendis.2025.101969","updated":null,"pmid":"42621153","pmcid":"PMC13486995","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC13486995/pdf","abstract":"During brain development, neural stem progenitor cells (NSPCs) and microglia interact within precise spatial niches; however, decoding mechanism is full of challenges using traditional analytical techniques. Here, we investigated the role of CCN1, a secreted protein enriched in NSPCs, using CNS-specific Ccn1 knockout mice. Through single cell RNA-seq analysis, we found that microglia were significantly reduced in the ventricular zone (VZ) at E17.5 and P2, with elevated expression of autophagy- and activation-related genes in Ccn1 -CKO mice. Spatial transcriptomics at P2 further showed that Ccn1 deletion region-specific redistributes microglia and leads to increased microglial aggregation and activation in the rostral lateral septum (LSR), alongside reductions in the VZ. Mechanistically, Ccn1 deletion in NSCs led to region-specific dysregulation of the key signaling ligands, Csf1 and Il2 . We found the elevated expression of Csf1 and Il2 specifically within the LSR region, which corresponded to the up-regulation of their respective receptors ( Csf1r , Cd53 ) and downstream targets ( Spp1 , Ctsb ) in LSR microglia, affecting microglial status. Our study reveals a region-specific NSC-microglia interaction regulated by Ccn1 , offering a new paradigm for understanding multicellular dynamics in brain development.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Spatial transcriptomics revealed the regulatory role of CCN1 to microglia distribution through region-specific cellular interactions\" by Bai Z, Chang Z, Wang S et al., https://doi.org/10.1016/j.gendis.2025.101969, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"single-cell-spatial","name":"Single-Cell & Spatial Omics","domain_slug":"biotech"}],"cited_in_dossiers":[]}