| First Author | Valenti G | Year | 2025 |
| Journal | Cell Rep | Volume | 44 |
| Issue | 6 | Pages | 115734 |
| PubMed ID | 40408246 | Mgi Jnum | J:367790 |
| Mgi Id | MGI:8211820 | Doi | 10.1016/j.celrep.2025.115734 |
| Citation | Valenti G, et al. (2025) Regulatory network analysis of Dclk1 gene expression reveals a tuft cell-ILC2 axis that inhibits pancreatic tumor progression. Cell Rep 44(6):115734 |
| abstractText | Doublecortin-like kinase 1 (Dclk1) expression identifies cells that are rare in normal pancreas but occur with an increased frequency in pancreatic neoplasia. The identity of these cells has been a matter of debate. We employed Dclk1 reporter mouse models and single-cell RNA sequencing (scRNA-seq) to define Dclk1-expressing cells. In normal pancreas, Dclk1 identifies subsets of ductal, islet, and acinar cells. In pancreatic neoplasia, Dclk1 identifies several cell populations, among which acinar-to-ductal metaplasia (ADM)-like cells and tuft-like cells are predominant. These two populations play opposing roles, with Dclk1(+) ADM-like cells sustaining and Dclk1(+) tuft-like cells restraining tumor progression. The generation of Dclk1(+) tuft-like cells requires the transcription factor SPIB and is sustained by a paracrine loop involving type 2 innate lymphoid cells (ILC2s) and cancer-associated fibroblasts (CAFs) that provide interleukin (IL)-13 and IL-33, respectively. Dclk1(+) tuft-like cells release angiotensinogen to restrain tumor progression. Overall, our study defines pancreatic Dclk1(+) cells and unveils a protective tuft cell-ILC2 axis against pancreatic neoplasia. |
