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Single-cell mapping identifies MSI+ cells as a common origin for diverse subtypes of pancreatic cancer.
- Source :
-
Cancer Cell . Nov2023, Vol. 41 Issue 11, p1989-1989. 1p. - Publication Year :
- 2023
-
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 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. [Display omitted] • Development of Msi2-Cre ERT2 knock-in mouse to express MYC in stem/progenitor cells • MSI2+ cells are cells of origin for multiple cancers such as lung, brain, and pancreas • Msi2-Myc mice form diverse pancreatic cancer subtypes from a common tumor precursor • Mapping dependencies of adenosquamous tumors identifies HMMR as a potential target Rajbhandari et al. report the development of a Msi2-Cre ERT2 mouse model which shows that multiple pancreatic cancer subtypes can arise from a common pool of MSI2+ cells and provides a powerful framework to understand the programs that shape divergent fates in pancreatic cancer. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 41
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 173474947
- Full Text :
- https://doi.org/10.1016/j.ccell.2023.09.008