Biology subjects

Pierreux, C. E.

Publications and source records attributed to Pierreux, C. E..

3 recordsLinked to original sources

bioRxiv2025

Acinar-Derived VEGF-A Orchestrates Blood Vascular Remodeling and Preserves Microvessels During Acute Pancreatitis

Acute pancreatitis is a common inflammatory condition of the pancreas that can lead to severe complications such as chronic pancreatitis and pancreatic ductal adenocarcinoma. While vascular remodeling is a hallmark of many inflammatory conditions, the molecular mechanisms underlying vascular changes during pancreatitis remain largely unexplored. This study aimed to investigate the vascular changes associated with acute pancreatitis and to identify the molecular mechanisms underlying these changes. Acute pancreatitis was induced in wild-type mice through caerulein injections and resulted in progressive and substantial vascular changes, characterized by morphological remodeling, increased vessel density, and elevated vascular permeability. These structural changes were accompanied by molecular alterations, including increased expression of endothelial genes and decreased surface expression of vascular endothelial VE-cadherin. Injured acinar cells exhibited a significant increase in VEGF-A expression during pancreatitis. Acinar-specific VEGF-A inactivation led to marked impairments in vascular remodeling, with reduced vessel density and diminished number of vessels, without affecting immune cell infiltration, fibrosis, or acinar-to-ductal metaplasia. Together, our work identifies a mechanism by which increased expression of VEGF-A by acinar cells during pancreatitis is essential for maintaining vascular integrity and for driving vascular remodeling in the inflamed pancreas.

pathology↗

bioRxiv2022

BRAFV600E expression in thyrocytes causes recruitment of immunosuppressive STABILIN-1 macrophages

Papillary thyroid carcinoma (PTC) is the most frequent histological subtype of thyroid cancers (TC), and BRAFV600E genetic alteration is found in 60% of this endocrine cancer. This oncogene is associated with poor prognosis, resistance to radioiodine therapy and tumor progression. Histological follow-up by anatomo-pathologists reveals that 2/3 of surgically-removed thyroids do not present malignant lesions. Continued fundamental research into the molecular mechanisms of TC downstream of BRAFV600E remains thus central to better understand the clinical behavior of these tumors. To study PTC, we used a mouse model in which expression of BRAFV600E is specifically switched on in thyrocytes by doxycycline administration. Upon daily intraperitoneal doxycycline injection, thyroid tissue rapidly acquired histological features mimicking human PTC. Transcriptomic analysis revealed major changes in immune signaling pathways upon BRAFV600E induction. Multiplex immunofluorescence confirmed the abundant recruitment of macrophages, among which a population of LYVE-1+/CD206+/STABILIN-1+ was dramatically increased. By genetically inactivating the gene coding for the scavenger receptor STABILIN-1, we showed an increase of CD8+ T cells in this in situ BRAFV600E dependent TC. Finally, we demonstrated the presence of CD206+/STABILIN-1+ macrophages in human thyroid pathologies. Altogether, we revealed the recruitment of immunosuppressive STABILIN-1 macrophages a PTC mouse model and the relevance of these observations in human thyroid tissues.

cancer biology↗

bioRxiv2022

Identification and implication of tissue-enriched ligands in epithelial-endothelial crosstalk during pancreas development

Development of the pancreas is driven by an intrinsic program coordinated with signals from other cell types in the epithelial environment. These intercellular communications have been so far challenging to study because of the low concentration, localized production and diversity of the signals released. Here, we combined scRNAseq data with a computational interactomic approach to identify signals involved in the reciprocal interactions between the various cell types of the developing pancreas. This in silico approach yielded 40,607 potential ligand-target interactions between the different main pancreatic cell types. Among this vast network of interactions, we focused on three ligands potentially involved in communications between epithelial and endothelial cells. Bmp7 and Wnt7b, expressed by pancreatic epithelial cells and predicted to target endothelial cells, and Sema6d, involved in the reverse interaction. In situ hybridization confirmed the localized expression of Bmp7 in the pancreatic epithelial tip cells and of Wnt7b in the trunk cells. On the contrary, Sema6d was enriched in endothelial cells. Functional experiments on ex vivo cultured pancreatic explants indicated that tip cell-produced Bmp7 restrained development of endothelial cells. This work identified ligands with a restricted tissular and cellular distribution and highlighted the role of Bmp7 in the intercellular communications shaping vessel development during pancreas organogenesis.

developmental biology↗