Laresgoiti, U;
Nikolić, MZ;
Rao, C;
Brady, JL;
Richardson, RV;
Batchen, EJ;
Chapman, KE;
(2016)
Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate.
Development
, 143
(20)
pp. 3686-3699.
10.1242/dev.134023.
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Abstract
Insufficient alveolar gas exchange capacity is a major contributor to lung disease. During lung development, a population of distal epithelial progenitors first produce bronchiolar-fated and subsequently alveolar-fated progeny. The mechanisms controlling this bronchiolar-to-alveolar developmental transition remain largely unknown. We developed a novel grafting assay to test if lung epithelial progenitors are intrinsically programmed or if alveolar cell identity is determined by environmental factors. These experiments revealed that embryonic lung epithelial identity is extrinsically determined. We show that both glucocorticoid and STAT3 signalling can control the timing of alveolar initiation, but that neither pathway is absolutely required for alveolar fate specification; rather, glucocorticoid receptor and STAT3 work in parallel to promote alveolar differentiation. Thus, developmental acquisition of lung alveolar fate is a robust process controlled by at least two independent extrinsic signalling inputs. Further elucidation of these pathways might provide therapeutic opportunities for restoring alveolar capacity.
| Type: | Article |
|---|---|
| Title: | Lung epithelial tip progenitors integrate glucocorticoid- and STAT3-mediated signals to control progeny fate. |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/dev.134023 |
| Publisher version: | http://dx.doi.org/10.1242/dev.134023 |
| Language: | English |
| Additional information: | © 2016. Published by The Company of Biologists Ltd This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
| Keywords: | Glucocorticoid, Human, Lung development, Mouse, STAT3, Adenoviridae, Alveolar Epithelial Cells, Animals, Cell Differentiation, Cells, Cultured, Epithelial Cells, Glucocorticoids, Humans, Lung, Mice, Mifepristone, Pulmonary Alveoli, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor, Signal Transduction, Stem Cells |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10051145 |
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