Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer
Recommended Citation
Salas-Escabillas DJ, Hoffman MT, Brender SM, Moore JS, Wen HJ, Benitz S, Davis ET, Long D, Wombwell AM, Chianis ERD, Allen-Petersen BL, Steele NG, Sears RC, Matsumoto I, DelGiorno KE, and Crawford HC. Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer. Dev Cell 2024.
Document Type
Article
Publication Date
12-19-2024
Publication Title
Developmental cell
Abstract
Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown. To determine the fate of mTCs during PDA progression, we created a dual recombinase lineage trace model, wherein a pancreas-specific FlpO was used to induce tumorigenesis, while a tuft-cell specific Pou2f3(CreERT/+) driver was used to induce expression of a tdTomato reporter. We found that mTCs in carcinoma transdifferentiate into neural-like progenitor cells (NRPs), a cell type associated with poor survival in patients. Using conditional knockout and overexpression systems, we found that Myc activity in mTCs is necessary and sufficient to induce this tuft-to-neuroendocrine transition (TNT).
PubMed ID
39721583
ePublication
ePub ahead of print
