Single cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single cell phenotypes have not been well defined. Combining single cell RNA and protein analytics in pancreatic cancer (PDAC) model systems, we demonstrated the role of stromal fibroblasts in shaping PDAC single cell heterogeneity towards invasive (EMT) and proliferative (PRO) phenotypes. Using highcontent digital imaging of RNA in situ hybridization in 195 tumors, we observed these EMT and PRO subpopulations in 319,626 individual cancer cells. Interestingly, we found these EMT and PRO subpopulations form distinct tumor gland “units” associated with differences in stromal abundance and patient survival. This demonstrates the impact of the stroma in shaping tumor architecture by altering inherent patterns of tumor glands in human PDAC.
Ligorio, Matteo and Sil, Srinjoy and Malagon-Lopez, Jose and Nieman, Linda T. and Misale, Sandra and Di Pilato, Mauro and Karabacak, Murat and Kulkarni, Anupriya S. and Jordan, Nicole Vincent and Franses, Joseph and Philipp, Julia and Kreuzer, Johannes and Desai, Niyati and Arora, Kshitij S. and Rajurkar, Mihir and Ebright, Richard Y. and Marangoni, Francesco and Boukhali, Myriam and Fatherree, Jackson P. and Tai, Eric and Vo, Kevin D. and Yashaswini, Chittampalli N. and Damon, Leah J. and Xega, Kristina and Desai, Rushil and Choz, Melissa and Bersani, Francesca and Morris, Robert and Thapar, Vishal and Rivera, Miguel N. and Deshpande, Vikram and Benes, Cyril H. and Maheswaran, Shyamala and Haber, Daniel A. and Fernandez-Del Castillo, Carlos and Ferrone, Cristina R. and Haas, Wilhelm and Aryee, Martin J. and Ting, David T., Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer (September 14, 2018). Available at SSRN: https://ssrn.com/abstract=3249464 or http://dx.doi.org/10.2139/ssrn.3249464
This version of the paper has not been formally peer reviewed.
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