Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration
Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cel...
Gespeichert in:
Veröffentlicht in: | Cell stem cell 2021-10, Vol.28 (10), p.1775-1789.e5 |
---|---|
Hauptverfasser: | , , , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1789.e5 |
---|---|
container_issue | 10 |
container_start_page | 1775 |
container_title | Cell stem cell |
container_volume | 28 |
creator | Penkala, Ian J. Liberti, Derek C. Pankin, Joshua Sivakumar, Aravind Kremp, Madison M. Jayachandran, Sowmya Katzen, Jeremy Leach, John P. Windmueller, Rebecca Stolz, Katharine Morley, Michael P. Babu, Apoorva Zhou, Su Frank, David B. Morrisey, Edward E. |
description | Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
[Display omitted]
•Alveolar type 1 cells exhibit plasticity after neonatal and adult hyperoxic injury•YAP/TAZ actively maintain alveolar type 1 cell identity•Ectopic nuclear YAP is insufficient to induce type 2 to type 1 cell differentiation
Penkala et al. investigate the effects of acute hyperoxic lung injury in neonatal and adult mice and demonstrate distinct, age-specific repair processes. They show that YAP/TAZ constrain type 1 cell identity and that the loss of these factors precipitates extensive alveolar type 1 to type 2 cell reprogramming. |
doi_str_mv | 10.1016/j.stem.2021.04.026 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8500919</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1934590921001843</els_id><sourcerecordid>2526144639</sourcerecordid><originalsourceid>FETCH-LOGICAL-c455t-ff68a89a5616eee248d2b32560df2de41986f1b032098e65e5ca27ab1e92e0613</originalsourceid><addsrcrecordid>eNp9kUFrHCEUx6WkNMm2X6CHMsdcZqqOOiOUQghtEgj00p56EFff7Lo4OlV3Id--LpuG5pKTgr_39733Q-gjwR3BRHzedbnA3FFMSYdZh6l4gy7IOPBWDsNwVu-yZy2XWJ6jy5x3GPOB4OEdOu97OTBJ-AX6fb2B1sICwUIojfYHiF6nBhZXtuCd9s3idS7OuPLYxGS2kEvSBXLj92HTbOMMMRedXW50sE2CDQSogIvhPXo7aZ_hw9O5Qr--f_t5c9c-_Li9v7l-aA3jvLTTJEY9Ss0FEQBA2WjpuqdcYDtRC4zIUUxkjXuK5QiCAzeaDnpNQFLAgvQr9PWUu-zXM1hTB0naqyW5WadHFbVTL1-C26pNPKiRYyzrklbo6ikgxT_7OqCaXTbgvQ4Q91lRTgVhTPRHlJ5Qk2LOCabnbwhWRytqp45W1NGKwkxVK7Xo0_8NPpf801CBLycA6poODpLKxkEwYF0CU5SN7rX8v4NooZg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2526144639</pqid></control><display><type>article</type><title>Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elsevier ScienceDirect Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Penkala, Ian J. ; Liberti, Derek C. ; Pankin, Joshua ; Sivakumar, Aravind ; Kremp, Madison M. ; Jayachandran, Sowmya ; Katzen, Jeremy ; Leach, John P. ; Windmueller, Rebecca ; Stolz, Katharine ; Morley, Michael P. ; Babu, Apoorva ; Zhou, Su ; Frank, David B. ; Morrisey, Edward E.</creator><creatorcontrib>Penkala, Ian J. ; Liberti, Derek C. ; Pankin, Joshua ; Sivakumar, Aravind ; Kremp, Madison M. ; Jayachandran, Sowmya ; Katzen, Jeremy ; Leach, John P. ; Windmueller, Rebecca ; Stolz, Katharine ; Morley, Michael P. ; Babu, Apoorva ; Zhou, Su ; Frank, David B. ; Morrisey, Edward E.</creatorcontrib><description>Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
[Display omitted]
•Alveolar type 1 cells exhibit plasticity after neonatal and adult hyperoxic injury•YAP/TAZ actively maintain alveolar type 1 cell identity•Ectopic nuclear YAP is insufficient to induce type 2 to type 1 cell differentiation
Penkala et al. investigate the effects of acute hyperoxic lung injury in neonatal and adult mice and demonstrate distinct, age-specific repair processes. They show that YAP/TAZ constrain type 1 cell identity and that the loss of these factors precipitates extensive alveolar type 1 to type 2 cell reprogramming.</description><identifier>ISSN: 1934-5909</identifier><identifier>EISSN: 1875-9777</identifier><identifier>DOI: 10.1016/j.stem.2021.04.026</identifier><identifier>PMID: 33974915</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alveolar Epithelial Cells ; alveolus ; Animals ; cellular plasticity ; Hippo ; Homeostasis ; Lung ; Mice ; regeneration ; Respiratory Mucosa ; Signal Transduction</subject><ispartof>Cell stem cell, 2021-10, Vol.28 (10), p.1775-1789.e5</ispartof><rights>2021 Elsevier Inc.</rights><rights>Copyright © 2021 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ff68a89a5616eee248d2b32560df2de41986f1b032098e65e5ca27ab1e92e0613</citedby><cites>FETCH-LOGICAL-c455t-ff68a89a5616eee248d2b32560df2de41986f1b032098e65e5ca27ab1e92e0613</cites><orcidid>0000-0003-3661-5261 ; 0000-0001-9628-042X ; 0000-0002-4932-2970</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1934590921001843$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33974915$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Penkala, Ian J.</creatorcontrib><creatorcontrib>Liberti, Derek C.</creatorcontrib><creatorcontrib>Pankin, Joshua</creatorcontrib><creatorcontrib>Sivakumar, Aravind</creatorcontrib><creatorcontrib>Kremp, Madison M.</creatorcontrib><creatorcontrib>Jayachandran, Sowmya</creatorcontrib><creatorcontrib>Katzen, Jeremy</creatorcontrib><creatorcontrib>Leach, John P.</creatorcontrib><creatorcontrib>Windmueller, Rebecca</creatorcontrib><creatorcontrib>Stolz, Katharine</creatorcontrib><creatorcontrib>Morley, Michael P.</creatorcontrib><creatorcontrib>Babu, Apoorva</creatorcontrib><creatorcontrib>Zhou, Su</creatorcontrib><creatorcontrib>Frank, David B.</creatorcontrib><creatorcontrib>Morrisey, Edward E.</creatorcontrib><title>Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration</title><title>Cell stem cell</title><addtitle>Cell Stem Cell</addtitle><description>Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
[Display omitted]
•Alveolar type 1 cells exhibit plasticity after neonatal and adult hyperoxic injury•YAP/TAZ actively maintain alveolar type 1 cell identity•Ectopic nuclear YAP is insufficient to induce type 2 to type 1 cell differentiation
Penkala et al. investigate the effects of acute hyperoxic lung injury in neonatal and adult mice and demonstrate distinct, age-specific repair processes. They show that YAP/TAZ constrain type 1 cell identity and that the loss of these factors precipitates extensive alveolar type 1 to type 2 cell reprogramming.</description><subject>Alveolar Epithelial Cells</subject><subject>alveolus</subject><subject>Animals</subject><subject>cellular plasticity</subject><subject>Hippo</subject><subject>Homeostasis</subject><subject>Lung</subject><subject>Mice</subject><subject>regeneration</subject><subject>Respiratory Mucosa</subject><subject>Signal Transduction</subject><issn>1934-5909</issn><issn>1875-9777</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFrHCEUx6WkNMm2X6CHMsdcZqqOOiOUQghtEgj00p56EFff7Lo4OlV3Id--LpuG5pKTgr_39733Q-gjwR3BRHzedbnA3FFMSYdZh6l4gy7IOPBWDsNwVu-yZy2XWJ6jy5x3GPOB4OEdOu97OTBJ-AX6fb2B1sICwUIojfYHiF6nBhZXtuCd9s3idS7OuPLYxGS2kEvSBXLj92HTbOMMMRedXW50sE2CDQSogIvhPXo7aZ_hw9O5Qr--f_t5c9c-_Li9v7l-aA3jvLTTJEY9Ss0FEQBA2WjpuqdcYDtRC4zIUUxkjXuK5QiCAzeaDnpNQFLAgvQr9PWUu-zXM1hTB0naqyW5WadHFbVTL1-C26pNPKiRYyzrklbo6ikgxT_7OqCaXTbgvQ4Q91lRTgVhTPRHlJ5Qk2LOCabnbwhWRytqp45W1NGKwkxVK7Xo0_8NPpf801CBLycA6poODpLKxkEwYF0CU5SN7rX8v4NooZg</recordid><startdate>20211007</startdate><enddate>20211007</enddate><creator>Penkala, Ian J.</creator><creator>Liberti, Derek C.</creator><creator>Pankin, Joshua</creator><creator>Sivakumar, Aravind</creator><creator>Kremp, Madison M.</creator><creator>Jayachandran, Sowmya</creator><creator>Katzen, Jeremy</creator><creator>Leach, John P.</creator><creator>Windmueller, Rebecca</creator><creator>Stolz, Katharine</creator><creator>Morley, Michael P.</creator><creator>Babu, Apoorva</creator><creator>Zhou, Su</creator><creator>Frank, David B.</creator><creator>Morrisey, Edward E.</creator><general>Elsevier Inc</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/0000-0003-3661-5261</orcidid><orcidid>https://orcid.org/0000-0001-9628-042X</orcidid><orcidid>https://orcid.org/0000-0002-4932-2970</orcidid></search><sort><creationdate>20211007</creationdate><title>Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration</title><author>Penkala, Ian J. ; Liberti, Derek C. ; Pankin, Joshua ; Sivakumar, Aravind ; Kremp, Madison M. ; Jayachandran, Sowmya ; Katzen, Jeremy ; Leach, John P. ; Windmueller, Rebecca ; Stolz, Katharine ; Morley, Michael P. ; Babu, Apoorva ; Zhou, Su ; Frank, David B. ; Morrisey, Edward E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-ff68a89a5616eee248d2b32560df2de41986f1b032098e65e5ca27ab1e92e0613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Alveolar Epithelial Cells</topic><topic>alveolus</topic><topic>Animals</topic><topic>cellular plasticity</topic><topic>Hippo</topic><topic>Homeostasis</topic><topic>Lung</topic><topic>Mice</topic><topic>regeneration</topic><topic>Respiratory Mucosa</topic><topic>Signal Transduction</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Penkala, Ian J.</creatorcontrib><creatorcontrib>Liberti, Derek C.</creatorcontrib><creatorcontrib>Pankin, Joshua</creatorcontrib><creatorcontrib>Sivakumar, Aravind</creatorcontrib><creatorcontrib>Kremp, Madison M.</creatorcontrib><creatorcontrib>Jayachandran, Sowmya</creatorcontrib><creatorcontrib>Katzen, Jeremy</creatorcontrib><creatorcontrib>Leach, John P.</creatorcontrib><creatorcontrib>Windmueller, Rebecca</creatorcontrib><creatorcontrib>Stolz, Katharine</creatorcontrib><creatorcontrib>Morley, Michael P.</creatorcontrib><creatorcontrib>Babu, Apoorva</creatorcontrib><creatorcontrib>Zhou, Su</creatorcontrib><creatorcontrib>Frank, David B.</creatorcontrib><creatorcontrib>Morrisey, Edward E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell stem cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Penkala, Ian J.</au><au>Liberti, Derek C.</au><au>Pankin, Joshua</au><au>Sivakumar, Aravind</au><au>Kremp, Madison M.</au><au>Jayachandran, Sowmya</au><au>Katzen, Jeremy</au><au>Leach, John P.</au><au>Windmueller, Rebecca</au><au>Stolz, Katharine</au><au>Morley, Michael P.</au><au>Babu, Apoorva</au><au>Zhou, Su</au><au>Frank, David B.</au><au>Morrisey, Edward E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration</atitle><jtitle>Cell stem cell</jtitle><addtitle>Cell Stem Cell</addtitle><date>2021-10-07</date><risdate>2021</risdate><volume>28</volume><issue>10</issue><spage>1775</spage><epage>1789.e5</epage><pages>1775-1789.e5</pages><issn>1934-5909</issn><eissn>1875-9777</eissn><abstract>Regeneration of the architecturally complex alveolar niche of the lung requires precise temporal and spatial control of epithelial cell behavior. Injury can lead to a permanent reduction in gas exchange surface area and respiratory function. Using mouse models, we show that alveolar type 1 (AT1) cell plasticity is a major and unappreciated mechanism that drives regeneration, beginning in the early postnatal period during alveolar maturation. Upon acute neonatal lung injury, AT1 cells reprogram into alveolar type 2 (AT2) cells, promoting alveolar regeneration. In contrast, the ability of AT2 cells to regenerate AT1 cells is restricted to the mature lung. Unbiased genomic assessment reveals that this previously unappreciated level of plasticity is governed by the preferential activity of Hippo signaling in the AT1 cell lineage. Thus, cellular plasticity is a temporally acquired trait of the alveolar epithelium and presents an alternative mode of tissue regeneration in the postnatal lung.
[Display omitted]
•Alveolar type 1 cells exhibit plasticity after neonatal and adult hyperoxic injury•YAP/TAZ actively maintain alveolar type 1 cell identity•Ectopic nuclear YAP is insufficient to induce type 2 to type 1 cell differentiation
Penkala et al. investigate the effects of acute hyperoxic lung injury in neonatal and adult mice and demonstrate distinct, age-specific repair processes. They show that YAP/TAZ constrain type 1 cell identity and that the loss of these factors precipitates extensive alveolar type 1 to type 2 cell reprogramming.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33974915</pmid><doi>10.1016/j.stem.2021.04.026</doi><orcidid>https://orcid.org/0000-0003-3661-5261</orcidid><orcidid>https://orcid.org/0000-0001-9628-042X</orcidid><orcidid>https://orcid.org/0000-0002-4932-2970</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1934-5909 |
ispartof | Cell stem cell, 2021-10, Vol.28 (10), p.1775-1789.e5 |
issn | 1934-5909 1875-9777 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8500919 |
source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals |
subjects | Alveolar Epithelial Cells alveolus Animals cellular plasticity Hippo Homeostasis Lung Mice regeneration Respiratory Mucosa Signal Transduction |
title | Age-dependent alveolar epithelial plasticity orchestrates lung homeostasis and regeneration |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T03%3A42%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Age-dependent%20alveolar%20epithelial%20plasticity%20orchestrates%20lung%20homeostasis%20and%20regeneration&rft.jtitle=Cell%20stem%20cell&rft.au=Penkala,%20Ian%20J.&rft.date=2021-10-07&rft.volume=28&rft.issue=10&rft.spage=1775&rft.epage=1789.e5&rft.pages=1775-1789.e5&rft.issn=1934-5909&rft.eissn=1875-9777&rft_id=info:doi/10.1016/j.stem.2021.04.026&rft_dat=%3Cproquest_pubme%3E2526144639%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2526144639&rft_id=info:pmid/33974915&rft_els_id=S1934590921001843&rfr_iscdi=true |