Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
07 2020
Historique:
received: 13 11 2019
accepted: 01 06 2020
entrez: 25 8 2020
pubmed: 25 8 2020
medline: 12 4 2022
Statut: epublish

Résumé

We provide a single-cell atlas of idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease, by profiling 312,928 cells from 32 IPF, 28 smoker and nonsmoker controls, and 18 chronic obstructive pulmonary disease (COPD) lungs. Among epithelial cells enriched in IPF, we identify a previously unidentified population of aberrant basaloid cells that coexpress basal epithelial, mesenchymal, senescence, and developmental markers and are located at the edge of myofibroblast foci in the IPF lung. Among vascular endothelial cells, we identify an ectopically expanded cell population transcriptomically identical to bronchial restricted vascular endothelial cells in IPF. We confirm the presence of both populations by immunohistochemistry and independent datasets. Among stromal cells, we identify IPF myofibroblasts and invasive fibroblasts with partially overlapping cells in control and COPD lungs. Last, we confirm previous findings of profibrotic macrophage populations in the IPF lung. Our comprehensive catalog reveals the complexity and diversity of aberrant cellular populations in IPF.

Identifiants

pubmed: 32832599
doi: 10.1126/sciadv.aba1983
pii: aba1983
pmc: PMC7439502
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eaba1983

Subventions

Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States
Organisme : NLM NIH HHS
ID : R21 LM012884
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL127349
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL145567
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL122626
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG008540
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL114501
Pays : United States

Informations de copyright

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Taylor S Adams (TS)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Jonas C Schupp (JC)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Sergio Poli (S)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Ehab A Ayaub (EA)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Nir Neumark (N)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.

Farida Ahangari (F)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Sarah G Chu (SG)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Benjamin A Raby (BA)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Pulmonary Medicine, Boston's Children Hospital, Harvard Medical School, Boston, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Giuseppe DeIuliis (G)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Michael Januszyk (M)

NuMedii, Inc., San Mateo, CA, USA.

Qiaonan Duan (Q)

NuMedii, Inc., San Mateo, CA, USA.

Heather A Arnett (HA)

NuMedii, Inc., San Mateo, CA, USA.

Asim Siddiqui (A)

NuMedii, Inc., San Mateo, CA, USA.

George R Washko (GR)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Robert Homer (R)

Department of Pathology, Yale School of Medicine, New Haven, CT, USA.
Pathology and Laboratory Medicine Service and VA CT HealthCare System, West Haven, CT, USA.

Xiting Yan (X)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

Ivan O Rosas (IO)

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Naftali Kaminski (N)

Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.

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Classifications MeSH