Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor
An evolutionarily conserved alveolar epithelial progenitor lineage that derives from alveolar type 2 cells is responsive to Wnt signalling and acts as a major facultative progenitor in regenerating the distal lung. A recipe for emergency alveoli The lung, which relies on complex distal gas exchange...
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| Veröffentlicht in: | Nature (London) 2018-03, Vol.555 (7695), p.251-255 |
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| creator | Zacharias, William J. Frank, David B. Zepp, Jarod A. Morley, Michael P. Alkhaleel, Farrah A. Kong, Jun Zhou, Su Cantu, Edward Morrisey, Edward E. |
| description | An evolutionarily conserved alveolar epithelial progenitor lineage that derives from alveolar type 2 cells is responsive to Wnt signalling and acts as a major facultative progenitor in regenerating the distal lung.
A recipe for emergency alveoli
The lung, which relies on complex distal gas exchange units called alveoli for its function, is a highly quiescent organ, displaying a very low turnover of cells in its normal state. However, it is prone to environmental and infectious damaging agents. Elucidating how organs that are maintained in a mainly quiescent state regenerate after injury could help in the development of therapeutic strategies to promote organ repair. Edward Morrisey and colleagues have identified and characterized an alveolar epithelial progenitor that is responsive to Wnt and FGF7 signalling triggered by injury and that exists in mouse and human adult lungs. The human alveolar epithelial progenitors can be isolated and grown in three-dimensional organoids, highlighting their potential for future regeneration strategies.
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration
1
; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration
2
,
3
. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies. |
| doi_str_mv | 10.1038/nature25786 |
| format | Article |
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A recipe for emergency alveoli
The lung, which relies on complex distal gas exchange units called alveoli for its function, is a highly quiescent organ, displaying a very low turnover of cells in its normal state. However, it is prone to environmental and infectious damaging agents. Elucidating how organs that are maintained in a mainly quiescent state regenerate after injury could help in the development of therapeutic strategies to promote organ repair. Edward Morrisey and colleagues have identified and characterized an alveolar epithelial progenitor that is responsive to Wnt and FGF7 signalling triggered by injury and that exists in mouse and human adult lungs. The human alveolar epithelial progenitors can be isolated and grown in three-dimensional organoids, highlighting their potential for future regeneration strategies.
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration
1
; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration
2
,
3
. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/nature25786</identifier><identifier>PMID: 29489752</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 38 ; 38/91 ; 631/136/2139 ; 631/532/489 ; 64 ; 64/60 ; Acute Lung Injury - pathology ; Acute Lung Injury - surgery ; Alveoli ; Animals ; Antigens, Surface - metabolism ; Axin Protein - metabolism ; Binding sites ; Bioinformatics ; Biomarkers - metabolism ; Cell Cycle ; Cell Lineage ; Cell surface ; Cells (biology) ; Chromatin - genetics ; Chromatin - metabolism ; Epigenomics ; Epithelial Cells - cytology ; Epithelial Cells - metabolism ; Epithelium ; Evolution, Molecular ; Female ; Fibroblast Growth Factors - metabolism ; Fibroblasts ; Gene expression ; Genomes ; Growth factors ; Health aspects ; Homeostasis ; Humanities and Social Sciences ; Humans ; Infections ; Influenza ; Injuries ; Intestine ; letter ; Lung ; Lungs ; Male ; Mice ; multidisciplinary ; Neoplasm Proteins - metabolism ; Observations ; Organoids ; Organoids - cytology ; Organoids - metabolism ; Organs ; Phenotypes ; Progenitor cells ; Proteins ; Pulmonary Alveoli - cytology ; Regeneration ; Regeneration (Biology) ; Restoration ; Rodents ; Science ; Signaling ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Surface markers ; Surfactants ; Tissue engineering ; Transcription factors ; Transcriptome ; Wnt protein ; Wnt Signaling Pathway</subject><ispartof>Nature (London), 2018-03, Vol.555 (7695), p.251-255</ispartof><rights>Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 2018</rights><rights>COPYRIGHT 2018 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Mar 8, 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c714t-f4853f295d3c4d6744e6562f4b4668980bab19aff352a42a4fd28684d7d2a8123</citedby><cites>FETCH-LOGICAL-c714t-f4853f295d3c4d6744e6562f4b4668980bab19aff352a42a4fd28684d7d2a8123</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature25786$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature25786$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,777,781,882,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29489752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zacharias, William J.</creatorcontrib><creatorcontrib>Frank, David B.</creatorcontrib><creatorcontrib>Zepp, Jarod A.</creatorcontrib><creatorcontrib>Morley, Michael P.</creatorcontrib><creatorcontrib>Alkhaleel, Farrah A.</creatorcontrib><creatorcontrib>Kong, Jun</creatorcontrib><creatorcontrib>Zhou, Su</creatorcontrib><creatorcontrib>Cantu, Edward</creatorcontrib><creatorcontrib>Morrisey, Edward E.</creatorcontrib><title>Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor</title><title>Nature (London)</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>An evolutionarily conserved alveolar epithelial progenitor lineage that derives from alveolar type 2 cells is responsive to Wnt signalling and acts as a major facultative progenitor in regenerating the distal lung.
A recipe for emergency alveoli
The lung, which relies on complex distal gas exchange units called alveoli for its function, is a highly quiescent organ, displaying a very low turnover of cells in its normal state. However, it is prone to environmental and infectious damaging agents. Elucidating how organs that are maintained in a mainly quiescent state regenerate after injury could help in the development of therapeutic strategies to promote organ repair. Edward Morrisey and colleagues have identified and characterized an alveolar epithelial progenitor that is responsive to Wnt and FGF7 signalling triggered by injury and that exists in mouse and human adult lungs. The human alveolar epithelial progenitors can be isolated and grown in three-dimensional organoids, highlighting their potential for future regeneration strategies.
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration
1
; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration
2
,
3
. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.</description><subject>13/100</subject><subject>38</subject><subject>38/91</subject><subject>631/136/2139</subject><subject>631/532/489</subject><subject>64</subject><subject>64/60</subject><subject>Acute Lung Injury - pathology</subject><subject>Acute Lung Injury - surgery</subject><subject>Alveoli</subject><subject>Animals</subject><subject>Antigens, Surface - metabolism</subject><subject>Axin Protein - metabolism</subject><subject>Binding sites</subject><subject>Bioinformatics</subject><subject>Biomarkers - metabolism</subject><subject>Cell Cycle</subject><subject>Cell Lineage</subject><subject>Cell surface</subject><subject>Cells (biology)</subject><subject>Chromatin - genetics</subject><subject>Chromatin - metabolism</subject><subject>Epigenomics</subject><subject>Epithelial Cells - cytology</subject><subject>Epithelial Cells - 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pathology</topic><topic>Acute Lung Injury - surgery</topic><topic>Alveoli</topic><topic>Animals</topic><topic>Antigens, Surface - metabolism</topic><topic>Axin Protein - metabolism</topic><topic>Binding sites</topic><topic>Bioinformatics</topic><topic>Biomarkers - metabolism</topic><topic>Cell Cycle</topic><topic>Cell Lineage</topic><topic>Cell surface</topic><topic>Cells (biology)</topic><topic>Chromatin - genetics</topic><topic>Chromatin - metabolism</topic><topic>Epigenomics</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelium</topic><topic>Evolution, Molecular</topic><topic>Female</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Fibroblasts</topic><topic>Gene expression</topic><topic>Genomes</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Infections</topic><topic>Influenza</topic><topic>Injuries</topic><topic>Intestine</topic><topic>letter</topic><topic>Lung</topic><topic>Lungs</topic><topic>Male</topic><topic>Mice</topic><topic>multidisciplinary</topic><topic>Neoplasm Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zacharias, William J.</au><au>Frank, David B.</au><au>Zepp, Jarod A.</au><au>Morley, Michael P.</au><au>Alkhaleel, Farrah A.</au><au>Kong, Jun</au><au>Zhou, Su</au><au>Cantu, Edward</au><au>Morrisey, Edward E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor</atitle><jtitle>Nature (London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2018-03-08</date><risdate>2018</risdate><volume>555</volume><issue>7695</issue><spage>251</spage><epage>255</epage><pages>251-255</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>An evolutionarily conserved alveolar epithelial progenitor lineage that derives from alveolar type 2 cells is responsive to Wnt signalling and acts as a major facultative progenitor in regenerating the distal lung.
A recipe for emergency alveoli
The lung, which relies on complex distal gas exchange units called alveoli for its function, is a highly quiescent organ, displaying a very low turnover of cells in its normal state. However, it is prone to environmental and infectious damaging agents. Elucidating how organs that are maintained in a mainly quiescent state regenerate after injury could help in the development of therapeutic strategies to promote organ repair. Edward Morrisey and colleagues have identified and characterized an alveolar epithelial progenitor that is responsive to Wnt and FGF7 signalling triggered by injury and that exists in mouse and human adult lungs. The human alveolar epithelial progenitors can be isolated and grown in three-dimensional organoids, highlighting their potential for future regeneration strategies.
Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration
1
; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration
2
,
3
. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>29489752</pmid><doi>10.1038/nature25786</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2018-03, Vol.555 (7695), p.251-255 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6020060 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 13/100 38 38/91 631/136/2139 631/532/489 64 64/60 Acute Lung Injury - pathology Acute Lung Injury - surgery Alveoli Animals Antigens, Surface - metabolism Axin Protein - metabolism Binding sites Bioinformatics Biomarkers - metabolism Cell Cycle Cell Lineage Cell surface Cells (biology) Chromatin - genetics Chromatin - metabolism Epigenomics Epithelial Cells - cytology Epithelial Cells - metabolism Epithelium Evolution, Molecular Female Fibroblast Growth Factors - metabolism Fibroblasts Gene expression Genomes Growth factors Health aspects Homeostasis Humanities and Social Sciences Humans Infections Influenza Injuries Intestine letter Lung Lungs Male Mice multidisciplinary Neoplasm Proteins - metabolism Observations Organoids Organoids - cytology Organoids - metabolism Organs Phenotypes Progenitor cells Proteins Pulmonary Alveoli - cytology Regeneration Regeneration (Biology) Restoration Rodents Science Signaling Stem cells Stem Cells - cytology Stem Cells - metabolism Surface markers Surfactants Tissue engineering Transcription factors Transcriptome Wnt protein Wnt Signaling Pathway |
| title | Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T10%3A05%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Regeneration%20of%20the%20lung%20alveolus%20by%20an%20evolutionarily%20conserved%20epithelial%20progenitor&rft.jtitle=Nature%20(London)&rft.au=Zacharias,%20William%20J.&rft.date=2018-03-08&rft.volume=555&rft.issue=7695&rft.spage=251&rft.epage=255&rft.pages=251-255&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/nature25786&rft_dat=%3Cgale_pubme%3EA530226115%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2012901926&rft_id=info:pmid/29489752&rft_galeid=A530226115&rfr_iscdi=true |