Cystic fibrosis (CF) affects multiple organs, including the pancreas, which sometimes leads to CF-related diabetes. Metabolic studies have demonstrated impaired β- and α-cell function in people with CF and pancreatic exocrine insufficiency, but the specific cellular changes remain unclear. Epithelial-to-mesenchymal transition (EMT) is a process commonly linked to pro-fibrotic pathologies. This study aimed to investigate EMT in pancreatic endocrine cells from subjects with and without CF.

From analysis of post-mortem pancreas tissue, Kattner et al. identified a previously unrecognised sub-population of α-cells which co-expressed vimentin (a classic mesenchymal marker) and glucagon, in subjects with and without CF. In donors without CF under 31 years, the frequency of these cells correlated positively with intra-islet collagen deposition, suggesting a possible role in tissue stress response or ageing. Single-cell RNA sequence analysis confirmed the presence of vimentin-positive (and -negative) α-cells in non-diabetic donors and in donors with chronic pancreatitis. Co-expressing cells retained normal α-cell gene signatures, but showed upregulation of genes related to extracellular matrix organisation, cell adhesion, migration, proliferation and stress resilience. 

This suggests that vimentin-expressing α-cells represent an intermediate epithelial/mesenchymal state, potentially facilitating α-cell adaptation to fibrosis, stress and ageing.

Read the full article in Journal of Endocrinology 264 e240190 https://doi.org/10.1530/JOE-24-0190.