Deletion of Slc9a1 in Cx3cr1⁺ cells stimulated microglial subcluster CREB1 signaling and microglia-oligodendrocyte crosstalk.

ABSTRACT: Microglial Na/H exchanger-1 (NHE1) protein, encoded by Slc9a1, plays a role in white matter demyelination of ischemic stroke brains. To explore underlying mechanisms, we conducted single cell RNA-seq transcriptome analysis in conditional Slc9a1 knockout (cKO) and wild-type (WT) mouse white matter tissues at 3 days post-stroke. Compared to WT, Nhe1 cKO brains expanded a microglial subgroup with elevated transcription of white matter myelination genes including Spp1, Lgals3, Gpnmb, and Fabp5. This subgroup also exhibited more acidic pH_i and significantly upregulated CREB signaling detected by ingenuity pathway analysis and flow cytometry. Moreover, the Nhe1 cKO white matter tissues showed enrichment of a corresponding oligodendrocyte subgroup, with pro-phagocytosis and lactate shu

SUBMITTER: Song S 

PROVIDER: S-EPMC10953158 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature