| First Author | Jiang Z | Year | 2023 |
| Journal | Cell Stem Cell | Volume | 30 |
| Issue | 8 | Pages | 1091-1109.e7 |
| PubMed ID | 37541213 | Mgi Jnum | J:338908 |
| Mgi Id | MGI:7518144 | Doi | 10.1016/j.stem.2023.07.002 |
| Citation | Jiang Z, et al. (2023) Tff2 defines transit-amplifying pancreatic acinar progenitors that lack regenerative potential and are protective against Kras-driven carcinogenesis. Cell Stem Cell 30(8):1091-1109.e7 |
| abstractText | While adult pancreatic stem cells are thought not to exist, it is now appreciated that the acinar compartment harbors progenitors, including tissue-repairing facultative progenitors (FPs). Here, we study a pancreatic acinar population marked by trefoil factor 2 (Tff2) expression. Long-term lineage tracing and single-cell RNA sequencing (scRNA-seq) analysis of Tff2-DTR-CreER(T2)-targeted cells defines a transit-amplifying progenitor (TAP) population that contributes to normal homeostasis. Following acute and chronic injury, Tff2(+) cells, distinct from FPs, undergo depopulation but are eventually replenished. At baseline, oncogenic Kras(G12D)-targeted Tff2(+) cells are resistant to PDAC initiation. However, Kras(G12D) activation in Tff2(+) cells leads to survival and clonal expansion following pancreatitis and a cancer stem/progenitor cell-like state. Selective ablation of Tff2(+) cells prior to Kras(G12D) activation in Mist1(+) acinar or Dclk1(+) FP cells results in enhanced tumorigenesis, which can be partially rescued by adenoviral Tff2 treatment. Together, Tff2 defines a pancreatic TAP population that protects against Kras-driven carcinogenesis. |
