Transcriptomic Profiling of Acutely Isolated Microglia after Experimental Subarachnoid Hemorrhage in a Conditional lpl Knockout Mouse Model
Subarachnoid hemorrhage (SAH) induces profound neuroinflammation, where microglial activation is a pivotal component of secondary brain injury. Lipoprotein lipase (Lpl) has been implicated in neuroinflammation and lipid metabolism within the brain, yet its cell-specific role in microglia following SAH is unknown. This study employs a microglia-specific conditional knockout strategy to define the transcriptomic role of LPL in the acute phase of SAH. We generated two mouse lines:Lpl(F/F) (control) and Cx3cr1;CreERT Lpl(F/F), in which tamoxifen administration induces Cre-mediated LPL deletion specifically in microglia. Experimental SAH was induced in both lines using the filament perforation model, with sham-operated animals as controls. At 72 hours post-SAH, a key time point for evolving injury and inflammation, microglia were acutely isolated from whole brains. A defined population (CD45^Low, CD11b^High) was purified via fluorescence-activated cell sorting (FACS) to ensure cellular homogeneity. Total RNA from these cells was processed using the SMART-seq2 protocol, a full-length, low-input RNA-seq method, to construct sequencing libraries. Sequencing was performed on the Illumina NovaSeq 6000 platform, generating 150 bp paired-end reads. The dataset comprises four experimental groups with biological replicates: Sham control (SO-CTR), Sham conditional knockout (SO-CKO), SAH control (SAH-CTR), and SAH conditional knockout (SAH-CKO). This resource provides a high-resolution, quantitative view of the microglial transcriptome, specifically enabling the dissection of Lpl-dependent and Lpl-independent gene expression changes during the subacute phase of SAH. It is valuable for identifying differentially expressed genes, signaling pathways, and regulatory networks underlying microglial responses in SAH, with potential to reveal novel mechanistic insights and therapeutic targets related to microglial lipid metabolism and inflammation.