Biology subjects

Bridgeman, V.

Publications and source records attributed to Bridgeman, V..

3 recordsLinked to original sources

bioRxiv2026

Sex-Dimorphic Neural Memory Shapes Pancreatic Tissue Resilience

Epithelial cells can encode prior damage into lasting epigenetic and functional states, enabling a primed response to future insults. In the pancreas, acute injury induces reversible acinar cell reprogramming toward a progenitor-like identity that persists beyond repair, supporting resilience to recurrent injury but creating a permissive state for malignant transformation. Given the central role of the tissue niche in stem cell regulation, we investigated microenvironmental adaptations that sustain this primed epithelial state. Using genetic mouse models and ex vivo organoid co-cultures, we identify a sex-specific sensory neural memory after pancreatitis that sustains long-term epithelial plasticity through a CGRP-dependent neuron-epithelial axis. We show that sex differences in acute inflammation drive neutrophil-dependent suppression of neural activation in females, decoupling neural memory from epithelial plasticity after repair. In males, neural memory promotes post-injury plasticity, revealing tissue memory as coordinated adaptation between epithelial progenitors and their niche.

cancer biology↗

bioRxiv2025

Cancer-driven neutrophil priming couples systemic epithelial regenerative programs with pre-metastatic niche formation

Cancer progression involves systemic changes that extend beyond the primary tumour. Through cancer-induced systemic conditioning, breast tumours generate subclinical alterations in distant organs that facilitate metastatic seeding and pre-metastatic niche formation. Neutrophils, mobilized through cancer-driven emergency granulopoiesis, actively contribute to this process. In this study we extend the concept of neutrophil-dependent conditioning beyond pre-metastatic sites, uncovering a broader systemic regenerative activation that links inflammation, tissue regeneration, and metastasis. This activation manifests as enhanced epithelial progenitor activity, measured by increased organoid formation, across multiple organs, including those with low risk of breast cancer metastasis. This neutrophil-dependent perturbation in lung alveolar progenitors and intestinal epithelial lineage commitment, is an indication of an altered organ physiology, enhancing tissue resilience to injury. Moreover, we identify UPP1 expression, which exclusively characterizes neutrophils generated through emergency granulopoiesis, as a key factor sustaining high translational activity in neutrophil progenitors and enabling the full acquisition of cancer-primed properties. Consequently, neutrophil loss of UPP1 reduces both their lung pro-metastatic function and their capacity to activate alveolar progenitors. Mechanistically, this involves interactions between cancer-primed neutrophils and platelets, which localize within lung interstitial spaces near alveolar cells to stimulate epithelial progenitor activity. Together, these findings uncover a previously unrecognized tumour-induced systemic conditioning in which neutrophils coordinate epithelial regenerative activation as part of a pro-metastatic epithelial niche, with UPP1 as a key determinant of their cancer-primed state.

cancer biology↗

bioRxiv2024

Type I interferons induced upon respiratory viral infection impair lung metastatic initiation

Invasive breast cancer accounts for 7% of all cancer-related deaths, with the lungs being a common site of metastases. At the same time, lower respiratory tract infections are a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce transitional changes in the lung; however, the impact of these changes on metastasis initiation and cancer progression remains unclear. Using primary murine MMTV-PyMT breast cancer cells in an experimental lung metastasis model, we show that changes induced by respiratory syncytial virus (RSV) infection impair tumor cell seeding and early establishment in the lung, resulting in lower number of metastatic nodules. Furthermore, we demonstrate that this reduction of metastases is due to alterations in the lung environment mediated by type I interferons (IFNs) that are produced in response to RSV infection. Consistent with that notion, intranasal administration of recombinant IFN- recapitulates the anti-tumor effect of RSV infection. Type I IFNs change the lung cellular composition and induce an Interferon Stimulated Gene (ISG) driven response, creating an alveolar environment that is less supportive of tumor cell growth. Indeed, epithelial cells from mice infected with RSV or intranasally exposed to IFN-, are less supportive of tumor cell growth ex vivo. Altogether, our results suggest that type I IFNs induced by infection with some respiratory viruses perturb the lungs and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization. SignificanceWomen diagnosed with metastatic breast cancer have a low survival rate. The lungs are a common metastatic site and are constantly exposed to viral pathogens, such as coronavirus, RSV and influenza virus. Thus, breast cancer and respiratory virus infection are likely to co-occur, but their interplay remains unclear. We show that type I interferons (IFNs), induced upon viral infection impair metastatic cancer cell seeding of mouse lungs. This is potentially via an effect of IFNs on lung epithelial cells, which become less supportive of early tumor cell proliferation. These findings indicate that viral infections and type I IFNs can alter the lung environment and impair implantation of metastatic cells, which could be explored to improve future cancer treatments.

immunology↗