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Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets
Kara J. Mould, … , Max Seibold, William J. Janssen
Kara J. Mould, … , Max Seibold, William J. Janssen
Published February 5, 2019
Citation Information: JCI Insight. 2019;4(5):e126556. https://doi.org/10.1172/jci.insight.126556.
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Research Article Immunology Pulmonology

Single cell RNA sequencing identifies unique inflammatory airspace macrophage subsets

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Abstract

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.

Authors

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

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Figure 7

Gene networks from bulk RNA-seq are coexpressed within single cell RNA-seq–based clusters.

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Gene networks from bulk RNA-seq are coexpressed within single cell RNA-s...
(A–G) Seven coexpressed gene networks derived from bulk RNA-seq data exhibit peak expression within single cell–derived resident (A–C) or recruited (D–G) macrophage clusters (see also Supplemental Figure 3). For each network, mean scaled eigengene expression is shown across bulk RNA-seq resident and recruited AMs from each day (heatmaps). For comparison with the single cell dataset, relative eigengene expression of each network is overlaid onto the single cell tSNE plot. Select results from pathway analysis of each network are shown in Table 1.

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