Intestinal tissue mechanics regulate angiogenesis and stem cell proliferation through endothelial Piezo

Phillips, Jade (2025) Intestinal tissue mechanics regulate angiogenesis and stem cell proliferation through endothelial Piezo. PhD thesis, University of Glasgow.

Abstract

The vasculature is an important component of stem cell niches, which is well characterised in many tissues. However, the angiocrine contribution to the intestinal stem cell niche remains largely understudied. Previously, our lab has uncovered an unrecognised crosstalk between the intestinal epithelium and the vasculature-like tracheal system in the fruit fly, Drosophila melanogaster. This is mediated by ROS and HIF-1 /FGF/FGFR signalling, which is necessary for tracheal remodelling and regenerative stem cell proliferation upon damage. However, we have also observed tracheal remodelling in contexts which are independant of ROS and therefore, this pathway alone is insufficient to justify the widely observed adaptation of the tracheal tissue to gut damage. As the vasculature is a very mechanosensitive tissue and the intestine undergoes significant morphological changes during regeneration, we hypothesised that mechanical changes induced in the intestine could contribute to tracheal remodelling and intestinal stem cell proliferation during regeneration and tumorigenesis. In my PhD work, I have found significant morphological changes in the intestinal epithelium which indicate altered cell mechanical state and upregulation of the mechanosensitive ion channel Piezo in the gut-associated tracheal system upon intestinal damage. Furthermore, in this thesis I show that Piezo is a regulator of previously described tracheal remodelling pathways through activation of Yki and find that the role of Piezo and the vascular intestinal stem cell niche is conserved between Drosophila and mammalian systems.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Supported by funding from Cancer Research UK (CRUK).
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Funder's Name: Cancer Research UK (CRUK)
• Supervisor's Name: Cordero, Professor Julia and Blyth, Professor Karen
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85643
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 10 Dec 2025 16:40
• Last Modified: 10 Dec 2025 16:43
• Thesis DOI: 10.5525/gla.thesis.85643
• URI: https://theses.gla.ac.uk/id/eprint/85643

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