Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets

JCI insight    

Kara J. Mould, Nathan D. Jackson, Peter M. Henson, Max Seibold, and William J. Janssen


Macrophages are well recognized for their dual roles in orchestrating inflammatory responses and regulating tissue repair. In almost all acutely inflamed tissues, 2 main subclasses of macrophages coexist. These include embryonically derived resident tissue macrophages and BM-derived recruited macrophages. While it is clear that macrophage subsets categorized in this fashion display distinct transcriptional and functional profiles, whether all cells within these categories and in the same inflammatory microenvironment share similar functions or whether further specialization exists has not been determined. To investigate inflammatory macrophage heterogeneity on a more granular level, we induced acute lung inflammation in mice and performed single cell RNA sequencing of macrophages isolated from the airspaces during health, peak inflammation, and resolution of inflammation. In doing so, we confirm that cell origin is the major determinant of alveolar macrophage (AM) programing, and, to our knowledge, we describe 2 previously uncharacterized, transcriptionally distinct subdivisions of AMs based on proliferative capacity and inflammatory programing.

Dataset information:

Genomic assay scRNA-seq Samples Alveolar MFs
Method for deriving gene sets Wilcoxon test Number of gene sets 5
Figure source Figure 6 Data source Supplemental table 11

Associated gene sets:

Gene set # Description No. of genes
1 Resident AM #1 29
2 Resident AM #2 27
3 Recruited AM Day 3 #1 28
4 Recruited AM Day 3 #2 29
5 Recruited AM Day 6 30

A total of 143 genes are associated with this dataset.