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Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis
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 previou...
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Published in: | Science advances 2020-07, Vol.6 (28), p.eaba1983-eaba1983 |
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creator | Adams, Taylor S Schupp, Jonas C Poli, Sergio Ayaub, Ehab A Neumark, Nir Ahangari, Farida Chu, Sarah G Raby, Benjamin A DeIuliis, Giuseppe Januszyk, Michael Duan, Qiaonan Arnett, Heather A Siddiqui, Asim Washko, George R Homer, Robert Yan, Xiting Rosas, Ivan O Kaminski, Naftali |
description | 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. |
doi_str_mv | 10.1126/sciadv.aba1983 |
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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.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.aba1983</identifier><identifier>PMID: 32832599</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Developmental Biology ; Diseases and Disorders ; Endothelial Cells ; Humans ; Idiopathic Pulmonary Fibrosis - genetics ; Lung ; Pulmonary Disease, Chronic Obstructive ; RNA-Seq ; SciAdv r-articles</subject><ispartof>Science advances, 2020-07, Vol.6 (28), p.eaba1983-eaba1983</ispartof><rights>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).</rights><rights>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). 2020 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-fe4d437306f29a022b577b0c9b5caea48d9a6acf050a42b641ed9e7b110f54ca3</citedby><cites>FETCH-LOGICAL-c456t-fe4d437306f29a022b577b0c9b5caea48d9a6acf050a42b641ed9e7b110f54ca3</cites><orcidid>0000-0002-5560-6136 ; 0000-0001-5442-3189 ; 0000-0001-8688-9004 ; 0000-0002-7714-8076 ; 0000-0002-8442-3312 ; 0000-0001-5917-4601 ; 0000-0003-2206-5748 ; 0000-0002-2055-5885 ; 0000-0003-4622-618X ; 0000-0002-4144-9395 ; 0000-0003-0841-8156 ; 0000-0003-4280-9070</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439502/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439502/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,730,783,787,888,2893,2894,27938,27939,53806,53808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32832599$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Adams, Taylor S</creatorcontrib><creatorcontrib>Schupp, Jonas C</creatorcontrib><creatorcontrib>Poli, Sergio</creatorcontrib><creatorcontrib>Ayaub, Ehab A</creatorcontrib><creatorcontrib>Neumark, Nir</creatorcontrib><creatorcontrib>Ahangari, Farida</creatorcontrib><creatorcontrib>Chu, Sarah G</creatorcontrib><creatorcontrib>Raby, Benjamin A</creatorcontrib><creatorcontrib>DeIuliis, Giuseppe</creatorcontrib><creatorcontrib>Januszyk, Michael</creatorcontrib><creatorcontrib>Duan, Qiaonan</creatorcontrib><creatorcontrib>Arnett, Heather A</creatorcontrib><creatorcontrib>Siddiqui, Asim</creatorcontrib><creatorcontrib>Washko, George R</creatorcontrib><creatorcontrib>Homer, Robert</creatorcontrib><creatorcontrib>Yan, Xiting</creatorcontrib><creatorcontrib>Rosas, Ivan O</creatorcontrib><creatorcontrib>Kaminski, Naftali</creatorcontrib><title>Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>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.</description><subject>Developmental Biology</subject><subject>Diseases and Disorders</subject><subject>Endothelial Cells</subject><subject>Humans</subject><subject>Idiopathic Pulmonary Fibrosis - genetics</subject><subject>Lung</subject><subject>Pulmonary Disease, Chronic Obstructive</subject><subject>RNA-Seq</subject><subject>SciAdv r-articles</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNpVUU1v1DAUtBAVrdpeOSIfuWTxZxJfkKqKAlIFUoGz9ey8bI2ydmonK_HvcbtLVU7Pz54Zz2gIecvZhnPRfig-wLDfgANuevmKnAnZ6UZo1b9-cT4ll6X8Zoxx1baamzfkVIpeCm3MGZl_hLidsPE4TfTu21VT8IFm3CNMhaJf0hw8hThQcJgzxIVOa9w2GUsYsG5PvDnN6wRLSLHQEGkYQpphua_Mer9LEfIfOgaXUwnlgpyMVRsvj_Oc_Lr59PP6S3P7_fPX66vbxivdLs2IalCyk6wdhQEmhNNd55g3TntAUP1goAU_Ms1ACdcqjoPBznHORq08yHPy8aA7r26Hg69mM0x2zmFX7dgEwf7_EsO93aa97ZQ0mokq8P4okNPDimWxu1Ae40LEtBYrlGz7Tne6r9DNAeprxJJxfP6GM_vYlD00ZY9NVcK7l-ae4f96kX8BlCiU0Q</recordid><startdate>20200701</startdate><enddate>20200701</enddate><creator>Adams, Taylor S</creator><creator>Schupp, Jonas C</creator><creator>Poli, Sergio</creator><creator>Ayaub, Ehab A</creator><creator>Neumark, Nir</creator><creator>Ahangari, Farida</creator><creator>Chu, Sarah G</creator><creator>Raby, Benjamin A</creator><creator>DeIuliis, Giuseppe</creator><creator>Januszyk, Michael</creator><creator>Duan, Qiaonan</creator><creator>Arnett, Heather A</creator><creator>Siddiqui, Asim</creator><creator>Washko, George R</creator><creator>Homer, Robert</creator><creator>Yan, Xiting</creator><creator>Rosas, Ivan O</creator><creator>Kaminski, Naftali</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5560-6136</orcidid><orcidid>https://orcid.org/0000-0001-5442-3189</orcidid><orcidid>https://orcid.org/0000-0001-8688-9004</orcidid><orcidid>https://orcid.org/0000-0002-7714-8076</orcidid><orcidid>https://orcid.org/0000-0002-8442-3312</orcidid><orcidid>https://orcid.org/0000-0001-5917-4601</orcidid><orcidid>https://orcid.org/0000-0003-2206-5748</orcidid><orcidid>https://orcid.org/0000-0002-2055-5885</orcidid><orcidid>https://orcid.org/0000-0003-4622-618X</orcidid><orcidid>https://orcid.org/0000-0002-4144-9395</orcidid><orcidid>https://orcid.org/0000-0003-0841-8156</orcidid><orcidid>https://orcid.org/0000-0003-4280-9070</orcidid></search><sort><creationdate>20200701</creationdate><title>Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis</title><author>Adams, Taylor S ; 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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. 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subjects | Developmental Biology Diseases and Disorders Endothelial Cells Humans Idiopathic Pulmonary Fibrosis - genetics Lung Pulmonary Disease, Chronic Obstructive RNA-Seq SciAdv r-articles |
title | Single-cell RNA-seq reveals ectopic and aberrant lung-resident cell populations in idiopathic pulmonary fibrosis |
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