| First Author | Rajbhandari N | Year | 2023 |
| Journal | Cancer Cell | Volume | 41 |
| Issue | 11 | Pages | 1989-2005.e9 |
| PubMed ID | 37802055 | Mgi Jnum | J:342146 |
| Mgi Id | MGI:7546672 | Doi | 10.1016/j.ccell.2023.09.008 |
| Citation | Rajbhandari N, et al. (2023) Single-cell mapping identifies MSI(+) cells as a common origin for diverse subtypes of pancreatic cancer. Cancer Cell |
| abstractText | Identifying the cells from which cancers arise is critical for understanding the molecular underpinnings of tumor evolution. To determine whether stem/progenitor cells can serve as cells of origin, we created a Msi2-Cre(ERT2) knock-in mouse. When crossed to CAG-LSL-Myc(T58A) mice, Msi2-Cre(ERT2) mice developed multiple pancreatic cancer subtypes: ductal, acinar, adenosquamous, and rare anaplastic tumors. Combining single-cell genomics with computational analysis of developmental states and lineage trajectories, we demonstrate that MYC preferentially triggers transformation of the most immature MSI2(+) pancreas cells into multi-lineage pre-cancer cells. These pre-cancer cells subsequently diverge to establish pancreatic cancer subtypes by activating distinct transcriptional programs and large-scale genomic changes, and enforced expression of specific signals like Ras can redirect subtype specification. This study shows that multiple pancreatic cancer subtypes can arise from a common pool of MSI2(+) cells and provides a powerful model to understand and control the programs that shape divergent fates in pancreatic cancer. |
