Single-Cell Sequencing Reveals an IRF3-dependent Immune and Remodeling Response in Wild Type Macrophages and Fibroblasts
- Author(s): Mercado, Amiel
- Advisor(s): King, Kevin R
- et al.
There is general consensus that immune cells such as macrophages within injured tissue influence remodeling and fibrosis. At the cellular level, this has been attributed to the communication between macrophages and fibroblasts. However, precisely how these communication is mediated at the molecular level remains unknown. We hypothesized fibroblasts are influenced by type I interferon signaling, either directly or indirectly via macrophages, which is a determining factor in the induction of adverse cardiac remodeling. In this study, differential gene expression analysis at a single cell level was done between wild type and knockout mice after myocardial infarction. It was found that a subset population of macrophages produce IRF3-dependent type I Interferon genes. Further, in fibroblasts, it was found matrix metalloproteinases is dominantly expressed in wild type. Given these results, this study proposes that the overexpression of matrix metalloproteinases in fibroblasts is linked to the production of the IRF3-dependent type I interferon genes in macrophages.