Pvf1-Pvr-mediated crosstalk between trachea and gut guides intestinal stem cell migration to promote gut regeneration

D. J. Mackay, A. John, C. F. Christensen, E. Connolly, R. Loudhaief, A. B. Tanari, M. Rauzi, J. Colombani () and D. S. Andersen ()
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D. J. Mackay: University of Copenhagen
A. John: University of Copenhagen
C. F. Christensen: University of Copenhagen
E. Connolly: University of Copenhagen
R. Loudhaief: University of Copenhagen
A. B. Tanari: iBV
M. Rauzi: iBV
J. Colombani: University of Copenhagen
D. S. Andersen: University of Copenhagen

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract In adult tissues, stem cells (SCs) reside in specialized niches, where they remain relatively stationary state until activated by injury. While migration is essential for regeneration, mechanisms guiding SCs towards injury sites remain poorly understood due to challenges in tracking them in vivo. Here, we present an experimental framework to monitor intestinal SC (ISC) movement in real time during early gut regeneration. We identify the Drosophila PDGF-VEGF-related receptor, Pvr, as a critical regulator of this process, with ISC-specific Pvr depletion strongly impairing migration and regeneration. The ligand, Pvf1, produced by gut-associated trachea after damage, serves as a guidance cue directing ISCs towards injury sites. Our work highlights a critical role of gut-trachea crosstalk in guiding ISC migration during regeneration. As neovascularization of injury sites is a key feature of tissue repair in both flies and mammals, these findings could have broader implications for regenerative processes across diverse adult tissues.

Date: 2025
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DOI: 10.1038/s41467-025-63704-8

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