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bioRxiv · 10.1101/2024.02.27.582358

High-dimensional mass cytometry reveals stemness state heterogeneity in pancreatic ductal adenocarcinoma

Ervin, E. H.·Ahern, D.·Liu, F.·Rendek, A.·Soonawalla, Z.·Oppermann, U.·Hulley, P.·Pauklin, S.
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Abstract

Stem-like cancer cells harbour high self-renewal capacity, exhibit enhanced tumourigenicity and have been associated with therapy resistance, metastasis and tumour relapse. Therefore, understanding the molecular features of stem-like cells is critical for targeting them effectively and improving treatment outcomes for cancer patients. Several markers have been used to isolate and study the putative stem-like cells of pancreatic ductal adenocarcinoma (PDAC), but the patterns of marker co-expression and overlap between identified individual subpopulations are yet to be comprehensively studied. Here we developed a mass cytometry antibody panel for simultaneous analysis of 33 stemness-associated markers at single-cell resolution. High-dimensional mass cytometry analysis of PDAC cell lines revealed molecularly heterogeneous stemness states and highlighted the role of genotype in determining the cell line-specific stemness signature. Stemness marker expression lie along a continuum in PDAC cell lines and patient samples indicative of stepwise phenotypic transitions. We also identified a subset of PDAC cells co-expressing high levels of Musashi-2, DCLK1 and CXCR4, and harbouring basal-like and EMT transcriptional programmes associated with highly plastic phenotype. This multiplexed analysis uncovers nuance and complexities of the stemness state in the PDAC.

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Ervin, E. H., Ahern, D., Liu, F., Rendek, A., Soonawalla, Z., Oppermann, U., Hulley, P., Pauklin, S.. 2024-03-01. High-dimensional mass cytometry reveals stemness state heterogeneity in pancreatic ductal adenocarcinoma. https://doi.org/10.1101/2024.02.27.582358

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