Systems genetics identifies a macrophage cholesterol network that associates with physiological wound healing

We generated a genomic and phenotypic resource comprising genetically outbred mice in which we measured (i) quantitative differences in wound healing indicated as ear area (ii) bone marrow derived macrophage (BMDM) mRNA expression by RNA-sequencing (RNA-seq), (iii) genome-wide SNPs genotyping by low-coverage sequencing.We performed gene co-expression network analysis and we identified a network in macrophages enriched in cholesterol genes which is genetically controlled by Runx2 gene. In vivo pharmacological blockage of Fasn with cerulenin showed delayed wound healing in rats and increased macrophage recruitment to the wound. We carried out RNA-sequencing in BMDMs from 146 outbred mice. We performed gene co-expression network analysis and we integrated the data with phenotipic data (wound healing) and with genotype.