Single-cell mapping identifies MSI⁺ cells as a common origin for diverse subtypes of pancreatic cancer.

ABSTRACT: 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 disti

SUBMITTER: Rajbhandari N 

PROVIDER: S-EPMC10836835 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature