Single-cell and bulk RNA sequencing reveals specific Trem2 positive B cell subtype niche after myocardial infarction in mice.

Abstract

This study aims to characterize B cell subtypes in mice following myocardial infarction (MI) and identify potential therapeutic targets for adverse remodeling post-MI. The scRNA-seq (GSE163129) and bulk RNA sequencing data (GSE19322) of mice post-MI were obtained from the GEO database. Seurat, gene set enrichment analysis, SCENIC analysis, Monocle 2 and NichNet analysis were performed in scRNA-seq data. Only the changes of immune cell populations in the infarct areas at different points after MI and pre - MI (steady - state) condition were compared. Bulk RNA-seq data for myocardium of post-MI in mice was used for validation. Twelve cell types were identified on scRNA-seq data and B cells were divided into five subtypes including B_Trem2 and others. B_Trem2 exhibited regulatory B (Breg) cells characteristics, displaying expressions of the cardiac repair gene Trem2, the anti-inflammatory marker Il10, and the myocardial remodeling molecule Spp1. B_Trem2 activated anti-inflammatory pathways. Nfe2l2, Rxrb, Zfp672, Prdm1 and Hivep3 were activated in the B_Trem2 subtype occupying the terminal stage of B cell development. Apoe was a potential activator of Spp1 overexpression in B_Trem2. Receptors of Apoe, namely Lrp1, Sdc4, and Sdc3, exhibited elevated expression within B_Trem2 subtype. This study identified a specific B cell subtype (B_Trem2) with Breg characteristics that overexpressed Spp1 in post- MI mice. Apoe may promote Spp1 expression in B_Trem2, by binding Apoe to Lrp1, Sdc4 and Sdc3 receptors on B_Trem2. This provides a new therapeutic target for MI.