Dynamic fibroblast-immune interactions shape recovery after brain injury [snRNASeq_Cxcl12]

Fibroblasts and immune cells coordinate tissue regeneration and necessary scarring after injury. In the brain, fibroblasts are border-enriched cells whose dynamic molecular states and immune interactions after injury remain unclear. We used single nuclear RNA sequencing at 21 days post photothrombotic (PT) injury to test the role of fibroblast-derived CXCL12 in regulating local immunity after brain injury. We find that loss of fibroblast CXCL12 causes dysregulated immune tone with elevated IFNg signaling. Tissue was collected from wildtype mice and mice with CXCL12-deficient fibroblasts [Col1a2(creER); Cxcl12(flox)]. Bulk lesional nuclei (DAPI+) were isolated and sort-purified from mice at 21 days post injury (dpi) for each condition. 1 male and 1 female mouse were harvested per timepoint/condition and were processed together.