Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Nature immunology - 20(2019), 2 vom: 14. Feb., Seite 163-172 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Aran, Dvir [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.05.2019 Date Revised 04.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41590-018-0276-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM292713568 |
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| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antigens, Differentiation, Myelomonocytic |2 NLM | |
| 650 | 7 | |a CX3C Chemokine Receptor 1 |2 NLM | |
| 650 | 7 | |a CX3CR1 protein, human |2 NLM | |
| 650 | 7 | |a Cx3cr1 protein, mouse |2 NLM | |
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| 700 | 1 | |a Looney, Agnieszka P |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Leqian |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Esther |e verfasserin |4 aut | |
| 700 | 1 | |a Fong, Valerie |e verfasserin |4 aut | |
| 700 | 1 | |a Hsu, Austin |e verfasserin |4 aut | |
| 700 | 1 | |a Chak, Suzanna |e verfasserin |4 aut | |
| 700 | 1 | |a Naikawadi, Ram P |e verfasserin |4 aut | |
| 700 | 1 | |a Wolters, Paul J |e verfasserin |4 aut | |
| 700 | 1 | |a Abate, Adam R |e verfasserin |4 aut | |
| 700 | 1 | |a Butte, Atul J |e verfasserin |4 aut | |
| 700 | 1 | |a Bhattacharya, Mallar |e verfasserin |4 aut | |
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