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Nat Immunol. 2019 Feb;20(2):163-172. doi: 10.1038/s41590-018-0276-y. Epub 2019 Jan 14.

Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.

Author information

1
Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA, USA.
2
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
3
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
4
Gladstone Institute of Cardiovascular Disease, San Francisco, CA, USA.
5
California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA, USA.
6
Chan Zuckerberg Biohub, San Francisco, CA, USA.
7
Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA. mallar.bhattacharya@ucsf.edu.

Abstract

Tissue fibrosis is a major cause of mortality that results from the deposition of matrix proteins by an activated mesenchyme. Macrophages accumulate in fibrosis, but the role of specific subgroups in supporting fibrogenesis has not been investigated in vivo. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the heterogeneity of macrophages in bleomycin-induced lung fibrosis in mice. A novel computational framework for the annotation of scRNA-seq by reference to bulk transcriptomes (SingleR) enabled the subclustering of macrophages and revealed a disease-associated subgroup with a transitional gene expression profile intermediate between monocyte-derived and alveolar macrophages. These CX3CR1+SiglecF+ transitional macrophages localized to the fibrotic niche and had a profibrotic effect in vivo. Human orthologs of genes expressed by the transitional macrophages were upregulated in samples from patients with idiopathic pulmonary fibrosis. Thus, we have identified a pathological subgroup of transitional macrophages that are required for the fibrotic response to injury.

PMID:
30643263
PMCID:
PMC6340744
DOI:
10.1038/s41590-018-0276-y
[Indexed for MEDLINE]
Free PMC Article

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