BACH1 orchestrates macrophage state transitions to coordinate regenerative inflammation [Individualmouse]

We identified BACH1 a heme-responsive transcriptional repressor, as a novel regulator of this process. Histological analysis reveals that Bach1 myeloid-specific knockout mice present a persistent necrotic fiber as well as delayed tissue repair while FACS and bulk RNA-seq show an abnormal macrophage phenotype switch and deregulation of critical genes involved in regenerative inflammation.

To study how BACH1 affects the macrophage subtype specification and cellular composition during muscle repair, we have performed single-cell RNA-seq (scRNA-seq) experiments in control and myeloid specific Bach1 knockout models at different time points post CTX injury in mice. Our results indicate significant differences in the macrophage subsets composition and gene expression profiles demonstrated by the magnitude of expression of critical inflammatory and repair-related genes.