Single-cell RNA sequencing identifies macrophage transcriptional heterogeneities in granulomatous diseases

ABSTRACT: Purpose: Using single-cell RNA sequencing to explore the common and unique pathways between progressive (SarcP) and remitting (SarcR) sarcoidosis as well as chronic beryllium disease (CBD) and sarcoidosis, focusing on macrophages and macrophages subpopulations (recruited vs. resident). Methods: We used scRNA-seq to analyze BAL cells from SarcP (N=2), SarcR (N=2), and CBD (N=3) compared to beryllium sensitized non-diseased subjects (BeS; N=2) or healthy control (Con; N=4). The controls were from Mould KJ, et al. Airspace Macrophages and Monocytes Exist in Transcriptionally Distinct Subsets in Healthy Adults. Am J Respir Crit Care Med 2020. We used the R package Seurat to project cells unto Uniform Manifold Approximation and Projection (UMAP) 2D space, identify cell clusters, and detect differentially expressed (DE) genes. Results: We focused our analysis on macrophages (excluding cell clusters going through the cell cycle). We first compared disease groups to healthy control Using False Discovery Rate (FDR) adjusted p<0.05 and absolute log fold change (log FC)>0.25. We identified 191, 242, and 234 DE genes within all macrophages for the comparisons of SarcP vs. Con, SarcR vs. Con, and CBD vs. Con, respectively, with 82 genes common to all three comparisons; 47 out of the 82 genes were common to all comparisons in regards to recruited macrophages. Conclusions: We focused this first single-cell transcriptome study in granulomatous lung disease on macrophages. This study offers investigators cell-specific transcriptional changes (genes and networks/pathways) to consider mechanisms of granulomatous disease and as potential drug targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE184735 | GEO | 2021/09/27

REPOSITORIES: GEO