About: Local lung hypoxia determines epithelial fate decisions during alveolar regeneration

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About: Local lung hypoxia determines epithelial fate decisions during alveolar regeneration Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Local lung hypoxia determines epithelial fate decisions during alveolar regeneration
Creator	Wei, Ying Matthay, Michael Xu, Jianming Gotts, Jeffrey Brumwell, Alexis Chapman, Harold Driver, Ian Jackson, Julia Kim, Thomas Lee, Dong-Kee Shannon, John Tan, Victor Vaughan, Andrew Xi, Ying
topic	covid:01c322116fb9f45a1baf5a6d8fce65388909243f#this
Source	PMC
abstract	After influenza infection, lineage-negative epithelial progenitors (LNEPs) exhibit a binary response to reconstitute epithelial barriers: activating a Notch-dependent ΔNp63/cytokeratin 5 (Krt5) remodelling program or differentiating into alveolar type II cells (AEC2s). Here we show that local lung hypoxia, through hypoxia-inducible factor (HIF1α), drives Notch signalling and Krt5(pos) basal-like cell expansion. Single-cell transcriptional profiling of human AEC2s from fibrotic lungs revealed a hypoxic subpopulation with activated Notch, suppressed surfactant protein C (SPC), and transdifferentiation toward a Krt5(pos) basal-like state. Activated murine Krt5(pos) LNEPs and diseased human AEC2s upregulate strikingly similar core pathways underlying migration and squamous metaplasia. While robust, HIF1α-driven metaplasia is ultimately inferior to AEC2 reconstitution in restoring normal lung function. HIF1α deletion or enhanced Wnt/β-catenin activity in Sox2(pos) LNEPs blocks Notch and Krt5 activation, instead promoting rapid AEC2 differentiation and migration and improving the quality of alveolar repair. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncb3580) contains supplementary material, which is available to authorized users.
has issue date	2017-07-24(xsd:dateTime)
bibo:doi	10.1038/ncb3580
bibo:pmid	28737769
has license	no-cc
sha1sum (hex)	01c322116fb9f45a1baf5a6d8fce65388909243f
schema:url	https://doi.org/10.1038/ncb3580
resource representing a document's title	Local lung hypoxia determines epithelial fate decisions during alveolar regeneration
has PubMed Central identifier	PMC5600325
has PubMed identifier	28737769
schema:publication	Nat Cell Biol
resource representing a document's body	covid:01c322116fb9f45a1baf5a6d8fce65388909243f#body_text
is http://vocab.deri.ie/void#inDataset of	proxy:http/ns.inria.fr/covid19/01c322116fb9f45a1baf5a6d8fce65388909243f
is schema:about of	named entity 'local' named entity 'fibrotic' named entity 'murine' named entity 'migration' named entity 'regeneration' covid:arg/01c322116fb9f45a1baf5a6d8fce65388909243f named entity 'epithelial' named entity 'pos' named entity 'Sox2' named entity 'upregulate' named entity 'improving' named entity 'binary' named entity 'ultimately' named entity 'Notch' named entity 'infection' named entity 'differentiating' named entity 'While' named entity 'Notch' named entity 'lung' named entity 'lungs' named entity 'protein' named entity 'squamous metaplasia' named entity 'Krt5' named entity 'Sox2' named entity 'alveolar' named entity 'HIF1α' named entity 'murine' named entity 'Krt5' named entity 'Notch signalling' named entity 'alveolar type II cells' named entity 'lung' named entity 'upregulate' named entity 'SPC' named entity 'hypoxia' named entity 'Triton X-100' named entity 'SAGM' named entity 'Sox2' named entity 'transdifferentiation' named entity 'Krt5' named entity 'epithelial' named entity 'CD14' named entity 'lung tissue' named entity 'infection' named entity 'epithelial' named entity 'Notch signalling' named entity 'Krt5' named entity 'motility' named entity 'binding sites' named entity 'RNF24' named entity 'SAGM' named entity 'PBS' named entity 'infection' named entity 'SAGM' named entity 'IPF' named entity 'receptor tyrosine kinases' named entity 'Krt5' named entity 'mRNA' named entity 'TLE3' named entity 'hypoxia' named entity 'Krt5' named entity 'TNFAIP2' named entity 'stem/progenitor cells' named entity 'Krt5' named entity 'lungs' named entity 'hypoxia' named entity 'epithelial'

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