# Spatial transcriptomics revealed the regulatory role of CCN1 to microglia distribution through region-specific cellular interactions

Article · 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

- Archive id: doi:10.1016/j.gendis.2025.101969
- Published: 2025-12-09
- Venue: Genes & diseases
- DOI: https://doi.org/10.1016/j.gendis.2025.101969
- PMID: 42621153
- PMCID: PMC13486995
- Citations: 0
- Source URL: https://doi.org/10.1016/j.gendis.2025.101969
- PDF: https://europepmc.org/articles/PMC13486995/pdf
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Single-Cell & Spatial Omics](https://space-kitty.com/topics/single-cell-spatial)

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