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

Nirakar Rajbhandari
University of California
January 1, 2023
Cancer Cell
https://pubmed.ncbi.nlm.nih.gov/37802055

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/37802055

Research summary

This study investigates the cellular origins of various pancreatic cancer subtypes using single-cell RNA sequencing and lineage tracing. The researchers identified Musashi-2 (MSI2) positive cells as a common progenitor for multiple pancreatic cancer subtypes, including ductal, acinar, and adenosquamous carcinomas. By employing a Knockin mouse model expressing CreERT2 under the control of the Msi2 promoter, they demonstrated that activation of oncogenic Myc in MSI2+ cells leads to the development of these diverse tumor types.

Key outcome of the study

Activation of oncogenic Myc in MSI2+ cells resulted in the formation of various pancreatic cancer subtypes, indicating that MSI2+ progenitor cells can give rise to diverse tumor lineages. Single-cell transcriptomic analysis revealed distinct differentiation trajectories leading to each subtype, providing insights into the cellular hierarchy and plasticity within pancreatic tumorigenesis.

Model

The study utilized an Msi2-CreERT2 Knockin mouse model, where the CreERT2 recombinase gene was inserted into the endogenous Msi2 locus. This genetic modification allowed for tamoxifen-inducible, MSI2-specific expression of CreERT2, enabling precise lineage tracing and targeted activation of oncogenes in MSI2+ cells.

TARGET:
Msi2
Synonyms:
Musashi-2

Keywords

Pancreatic cancer, Cancer stem cells, Tumor heterogeneity, Lineage tracing, Single-cell RNA sequencing

Technical specifications

Knockin mouse model, Msi2 promoter, CreERT2 system, Tamoxifen-inducible recombination, Oncogene activation

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