2017
DOI: 10.1002/stem.2744
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Notch Signaling Controls Transdifferentiation of Pulmonary Neuroendocrine Cells in Response to Lung Injury

Abstract: Production of an appropriate number of distinct cell types in precise locations during embryonic development is critical for proper tissue function. Homeostatic renewal or repair of damaged tissues in adults also requires cell expansion and transdifferentiation to replenish lost cells. However, the responses of diverse cell types to tissue injury are not fully elucidated. Moreover, the molecular mechanisms underlying transdifferentiation remain poorly understood. This knowledge is essential for harnessing the … Show more

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Cited by 52 publications
(34 citation statements)
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“…Naphthalene injury was performed 4 weeks after the last dose of tamoxifen, which clarified that non-PNECs do not contribute to the Cgrp CreER lineage. Furthermore, Notchbut not Hedgehog or Yapsignaling regulates the transdifferentiation of PNECs into club and ciliated cells during regeneration (Yao et al, 2018). In addition, Notch enhancement seems to induce the dedifferentiation and proliferation of PNECs after injury (Yao et al, 2018).…”
mentioning
confidence: 99%
“…Naphthalene injury was performed 4 weeks after the last dose of tamoxifen, which clarified that non-PNECs do not contribute to the Cgrp CreER lineage. Furthermore, Notchbut not Hedgehog or Yapsignaling regulates the transdifferentiation of PNECs into club and ciliated cells during regeneration (Yao et al, 2018). In addition, Notch enhancement seems to induce the dedifferentiation and proliferation of PNECs after injury (Yao et al, 2018).…”
mentioning
confidence: 99%
“…This was confirmed by lineage tracing using Calca creER , where lineaged PNECs can indeed give rise to not only club cells but also ciliated cells after naphthalene treatment (Song et al, 2012). In recent studies, epithelial injury led to an increase in Notch signaling in proliferating PNECs (Yao et al, 2018). scRNA-seq identified a subset of PNECs marked by Notch2, which can dedifferentiate and then re-differentiate into other airway epithelial cell types, post injury (Ouadah et al, 2019).…”
Section: Pnecs Function As Progenitor Cells and Progenitor Nichesmentioning
confidence: 80%
“…There are a number of factors that may influence this including exposure to a more hypoxic environment upregulating hypoxia response genes such as HIF-1a and HIF-2a causing an upregulation of Notch signaling, as previously reported (Gerovac et al, 2014). Notch upregulation, in turn, is known to be antagonistic toward PNEC fate induction (Yao et al, 2018). Existing literature has not specifically indicated a requirement for an ALI during differentiation to generate PNEC-like cells Konishi et al, 2016).…”
Section: Discussionmentioning
confidence: 93%