scRNA-seq of aortic arches from smooth muscle cell–specific Hif1a knockout and control mice with atherosclerosis
Smooth muscle cells (SMCs) undergo phenotypic switching during atherosclerosis and give rise to a large fraction of plaque cells. To investigate the role of hypoxia-inducible factor 1a (HIF1a) signaling in SMC behaviour during atherogenesis, we used mice in which Hif1a is conditionally deleted in lineage-traced SMCs (Myh11-CreERT2; Rosa26-tdTomato; Hif1a-floxed). Cre recombination was induced with tamoxifen at 6 weeks of age. Atherosclerosis was induced by a single tail-vein injection of rAAV8-PCSK9 at 9 weeks of age followed by 21 weeks of high-fat diet feeding. Aortic arches were pooled by genotype from SMC-specific Hif1a knockout (Hif1aSMC-KO, n=8) and wild-type control (Hif1aWT, n=6) male mice, enzymatically dissociated, and viable cells (Draq5+/DAPI–) isolated by fluorescence-activated cell sorting. Single-cell transcriptomes were generated using the 10x Genomics Chromium Next GEM Single Cell 3' v3.1 platform and sequenced on an Illumina HiSeq 4000. Reads were aligned to the mm10 reference transcriptome supplemented with the tdTomato transgene sequence using Cell Ranger. The dataset enables comparison of cell-type composition and of SMC-derived cell transcriptional states between genotypes, with a focus on hypoxia- and stress-response pathways underlying SMC phenotypic modulation. Only male mice were studied because the Myh11-CreERT2 transgene is Y-linked.
Smooth muscle cells (SMCs) undergo phenotypic switching during atherosclerosis and give rise to a large fraction of plaque cells. To investigate the role of hypoxia-inducible factor 1a (HIF1a) signaling in SMC behaviour during atherogenesis, we used mice in which Hif1a is conditionally deleted in lineage-traced SMCs (Myh11-CreERT2; Rosa26-tdTomato; Hif1a-floxed). Cre recombination was induced with tamoxifen at 6 weeks of age. Atherosclerosis was induced by a single tail-vein injection of rAAV8-PCSK9 at 9 weeks of age followed by 21 weeks of high-fat diet feeding. Aortic arches were pooled by genotype from SMC-specific Hif1a knockout (Hif1aSMC-KO, n=8) and wild-type control (Hif1aWT, n=6) male mice, enzymatically dissociated, and viable cells (Draq5+/DAPI–) isolated by fluorescence-activated cell sorting. Single-cell transcriptomes were generated using the 10x Genomics Chromium Next GEM Single Cell 3' v3.1 platform and sequenced on an Illumina HiSeq 4000. Reads were aligned to the mm10 reference transcriptome supplemented with the tdTomato transgene sequence using Cell Ranger. The dataset enables comparison of cell-type composition and of SMC-derived cell transcriptional states between genotypes, with a focus on hypoxia- and stress-response pathways underlying SMC phenotypic modulation. Only male mice were studied because the Myh11-CreERT2 transgene is Y-linked.
European Bioinformatics Institute