Ccn1 regulates the spatial expression of Csf1 and Il2 to influence NSC-microglia interactions (IMAGE)
Caption
(A) Overview of the NicheNet analysis framework for investigating NSC-microglia interactions. (B) Prioritized ligand-receptor pairs from neural stem progenitor cells (NSPCs) to LSR microglia in wild type (WT) versus conditional knockout (CKO). Heatmaps display condition-specific min log2 FC of NSPC ligands (left) and lateral sub-region (LSR) microglia receptors (right) relative to the opposite niche. Red indicates higher specificity; blue indicates lower specificity (NicheNet analysis). (C) Heatmaps showing the regulatory potential of prioritized ligands in NSPCs and their predicted target genes in LSR microglia, based on spatial transcriptomic data (NicheNet analysis). (D) Ligand activity analysis of prioritized ligands in LSR microglia from spatial transcriptomic data (NicheNet analysis). (E) Normalized expression levels of Csf1 and Il2 in NSPCs located in ventricular zone (VZ) and LSR regions of WT and CKO mice, revealed by spatial transcriptomic analysis. (F) Normalized spatial expression of Csf1 and Il2 in astrocytes located in VZ and LSR regions of WT and CKO mice, based on spatial transcriptomic analysis. (G) Normalized spatial expression of corresponding receptors in microglia at VZ and LSR regions, analyzed from spatial transcriptomic data. (H) Proposed regulatory mechanisms involving the Il2-Cd25 and Csf1-Csf1r pathways and their target genes. Il2 positively regulates the downstream ligand Cd53, enhancing expression of target genes (e.g., Ctsb, Spp1). Csf1 positively regulates its receptor Csf1r, promoting expression of target genes (e.g., Ctsb, Spp1). (I) Spatial co-expression patterns of Il2 (ligand) and Spp1 (target) in NSPCs and microglia in WT and CKO brains (spatial transcriptomic analysis). (J) Spatial co-expression patterns of Csf1 (ligand) and Ctsb (target) in NSPCs and microglia in WT and CKO brains (spatial transcriptomic analysis). (K) Expression levels of representative target genes in microglia from VZ and LSR regions of WT versus CKO mice (spatial transcriptomic analysis). (L, M) Upregulation of Spp1 in LSR microglia of P2 CKO mice was confirmed by in situ sequencing (ISS) signal (L) and statistical analysis (M).
Credit
Zhile Bai, Zhanhe Chang, Shuguang Wang, Jiangli Zheng, Huan Wu, Hanyu Liu, Yalin Zhang, Jiayang Xie, Qingran Bai, Jiqing Yin, You Wu, Qin Shen, Shaorong Gao, Yawei Gao
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