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    A conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs

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    Authors
    Shue, Y. T.
    Drainas, A. P.
    Li, N. Y.
    Pearsall, Sarah M
    Morgan, Derrick
    Sinnott-Armstrong, N.
    Hipkins, S. Q.
    Coles, G. L.
    Lim, J. S.
    Oro, A. E.
    Simpson, Kathryn L
    Dive, Caroline
    Sage, J.
    Show allShow less
    Affiliation
    Departments of Pediatrics, Stanford University, Stanford, CA, USA
    Issue Date
    2022
    
    Metadata
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    Abstract
    The Notch pathway is a conserved cell-cell communication pathway that controls cell fate decisions. Here we sought to determine how Notch pathway activation inhibits the neuroendocrine cell fate in the lungs, an archetypal process for cell fate decisions orchestrated by Notch signaling that has remained poorly understood at the molecular level. Using intratumoral heterogeneity in small-cell lung cancer as a tractable model system, we uncovered a role for the transcriptional regulators REST and YAP as promoters of the neuroendocrine to non-neuroendocrine transition. We further identified the specific neuroendocrine gene programs repressed by REST downstream of Notch in this process. Importantly, we validated the importance of REST and YAP in neuroendocrine to non-neuroendocrine cell fate switches in both developmental and tissue repair processes in the lungs. Altogether, these experiments identify conserved roles for REST and YAP in Notch-driven inhibition of the neuroendocrine cell fate in embryonic lungs, adult lungs, and lung cancer.
    Citation
    Shue YT, Drainas AP, Li NY, Pearsall SM, Morgan D, Sinnott-Armstrong N, et al. A conserved YAP/Notch/REST network controls the neuroendocrine cell fate in the lungs. Vol. 13, Nature Communications. Springer Science and Business Media LLC; 2022. 
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/625315
    DOI
    10.1038/s41467-022-30416-2
    PubMed ID
    35577801
    Additional Links
    https://dx.doi.org/10.1038/s41467-022-30416-2
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-022-30416-2
    Scopus Count
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