Figure 1 from Dynamic Evolution of Fibroblasts Revealed by Single-Cell RNA Sequencing of Human Pancreatic Cancer

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posted on 2025-04-03, 21:48 authored by Slavica Dimitrieva, Jon M. Harrison, Jonathan Chang, Michelle Piquet, Mari Mino-Kenudson, Millicent Gabriel, Vivek Sagar, Heiko Horn, Kasper Lage, Julie Kim, Gang Li, Shaobu Weng, Cynthia Harris, Anupriya S. Kulkarni, David T. Ting, Motaz Qadan, Peter J. Fagenholz, Cristina R. Ferrone, Angelo L. Grauel, Tyler Laszewski, Alina Raza, Markus Riester, Tim Somerville, Joel P. Wagner, Glenn Dranoff, Jeffrey A. Engelman, Audrey Kauffmann, Rebecca Leary, Andrew L. Warshaw, Keith D. Lillemoe, Carlos Fernández-del Castillo, David A. Ruddy, Andrew S. Liss, Viviana Cremasco

scRNA-seq of human pancreatic tissues. A, Schematic representation of the types of tissues employed in this study and the experimental pipeline for their analysis by scRNA-seq. B, UMAP visualization of single cells from all samples colored by cell type. C, UMAP projections of single cells from each tissue type (colored) contributing to the global UMAP (gray). D, Representative images of H&E-stained sections of each tissue type. Scale bar, 100 μm. E, Quantification of cell types within each tissue type. F, Quantification of cell populations (% from the total) along with the number of DE genes in each cell population between tissue types. UMAP, Uniform Manifold Approximation and Projection for Dimension Reduction; H&E, hematoxylin and eosin.

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ARTICLE ABSTRACT

Cancer progression and response to therapy are inextricably reliant on the coevolution of a supportive tissue microenvironment. This is particularly evident in pancreatic ductal adenocarcinoma, a tumor type characterized by expansive and heterogeneous stroma. Herein, we employed single-cell RNA sequencing and spatial transcriptomics of normal, inflamed, and malignant pancreatic tissues to contextualize stromal dynamics associated with disease and treatment status, identifying temporal and spatial trajectories of fibroblast differentiation. Using analytical tools to infer cellular communication, together with a newly developed assay to annotate genomic alterations in cancer cells, we additionally explored the complex intercellular networks underlying tissue circuitry, highlighting a fibroblast-centric interactome that grows in strength and complexity in the context of malignant transformation. Our study yields new insights on the stromal remodeling events favoring the development of a tumor-supportive microenvironment and provides a powerful resource for the exploration of novel points of therapeutic intervention in pancreatic ductal adenocarcinoma. Pancreatic cancer remains a high unmet medical need. Understanding the interactions between stroma and cancer cells in this disease may unveil new opportunities for therapeutic intervention.

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Keywords

Tumor Microenvironment Tumor-stromal cell interactions Gastrointestinal Cancers Pancreatic cancer Single Cell Technologies

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CC BY