Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila

Perochon, J. , Yu, Y., Aughey, G. N., Medina, A. B., Southall, T. D. and Cordero, J. B. (2021) Dynamic adult tracheal plasticity drives stem cell adaptation to changes in intestinal homeostasis in Drosophila. Nature Cell Biology, 23(5), pp. 485-496. (doi: 10.1038/s41556-021-00676-z) (PMID:33972729) (PMCID:PMC7610788)

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Coordination of stem cell function by local and niche-derived signals is essential to preserve adult tissue homeostasis and organismal health. The vasculature is a prominent component of multiple stem cell niches. However, its role in adult intestinal homeostasis remains largely understudied. Here we uncover a previously unrecognised crosstalk between adult intestinal stem cells in Drosophila and the vasculature-like tracheal system, which is essential for intestinal regeneration. Following damage to the intestinal epithelium, gut-derived reactive oxygen species activate tracheal HIF-1α and bidirectional FGF/FGFR signalling, leading to reversible remodelling of gut-associated terminal tracheal cells and intestinal stem cell proliferation following damage. Unexpectedly, reactive oxygen species-induced adult tracheal plasticity involves downregulation of the tracheal specification factor trachealess (trh) and upregulation of IGF2 messenger RNA-binding protein (IGF2BP2/Imp). Our results reveal an intestine–vasculature inter-organ communication programme that is essential to adapt the stem cell response to the proliferative demands of the intestinal epithelium.

Item Type:Articles
Additional Information:J.P. and J.B.C. are funded by a Wellcome Trust and Royal Society Sir Henry Dale Fellowship (grant no. 104103/Z/14/Z; J.B.C.) and a Wellcome Trust Institutional Strategic Support Fund (ISSF)−Excellence and Innovation Catalyst Award to J.B.C. J.P. was partly funded by a BBSRC−Flexible Talent Mobility Account (FTMA) Award (grant no. BB/R506576/1). Y.Y. and A.B.M. are funded by CRUK core funding to the CRUK Beatson Institute (grant no. A17196). T.D.S. and G.N.A. were funded by a Wellcome Trust Investigator grant (grant no. 104567; T.D.S.) and a BBSRC grant (grant no. BB/ P017924/1; T.D.S. and G.N.A.).
Glasgow Author(s) Enlighten ID:Yu, Dr Yachuan and Medina, André and Perochon, Miss Jessica and Cordero, Professor Julia
Authors: Perochon, J., Yu, Y., Aughey, G. N., Medina, A. B., Southall, T. D., and Cordero, J. B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature Cell Biology
Publisher:Nature Research
ISSN (Online):1476-4679
Published Online:10 May 2021
Copyright Holders:Copyright © 2021 Springer Nature
First Published:First published in Nature Cell Biology 23(5): 485-496
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190860Regulation of stem cell function during tissue homeostasis and transformationJulia CorderoWellcome Trust (WELLCOTR)104103/Z/14/ZInstitute of Cancer Sciences
302024Flexible Talent Mobility AccountsCarl GoodyearBiotechnology and Biological Sciences Research Council (BBSRC)BB/R506576/1III - Immunology