Lung epithelial tip progenitors integrate Glucocorticoid and STAT3-mediated signals to control progeny fate
Brady, Jane L
Richardson, Rachel V
Batchen, Emma J
Chapman, Karen E
The Company of Biologists
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Laresgoiti, U., Nikolić, M., Rao, C., Brady, J. L., Richardson, R. V., Batchen, E. J., Chapman, K. E., & et al. (2016). Lung epithelial tip progenitors integrate Glucocorticoid and STAT3-mediated signals to control progeny fate. Development https://doi.org/10.1242/dev.134023
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 may provide therapeutic opportunities for restoring alveolar capacity.
glucocorticoid, Stat3, mouse, human, lung development
Medical Research Council (G0900424, ER), the March of Dimes (5-FY11-119, ER), the Wellcome Trust (093029, ER), Newton Trust (14.07h, ER), Wellcome Trust PhD programme for Clinicians (MN), Postdoctoral Fellowship from the Government of the Basque Country (UL), MRC studentship (RVR), British Heart Foundation Studentship (EJB), COST BM1201. Core grants from the Wellcome Trust (092096) and Cancer Research UK (C6946/A14492).
External DOI: https://doi.org/10.1242/dev.134023
This record's URL: https://www.repository.cam.ac.uk/handle/1810/260645
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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