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Supplementary Tables from Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions

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posted on 2023-05-17, 13:20 authored by Eileen S. Carpenter, Ahmed M. Elhossiny, Padma Kadiyala, Jay Li, Jake McGue, Brian D. Griffith, Yaqing Zhang, Jacob Edwards, Sarah Nelson, Fatima Lima, Katelyn L. Donahue, Wenting Du, Allison C. Bischoff, Danyah Alomari, Hannah R. Watkoske, Michael Mattea, Stephanie The, Carlos E. Espinoza, Meredith Barrett, Christopher J. Sonnenday, Nicholas Olden, Chin-Tung Chen, Nicole Peterson, Valerie Gunchick, Vaibhav Sahai, Arvind Rao, Filip Bednar, Jiaqi Shi, Timothy L. Frankel, Marina Pasca di Magliano

Supplemental Table 1: Demographics and clinical data for donor Gife of Life Samples Supplemental Table 2: Putative Ligand-Receptor pairs comparing all cell types from single cell sequencing of tumor samples compared to healthy samples. Supplemental Table 3: Differential gene expression using linear mixed model analysis of cell types from spatial transcriptomic ROIs. Supplemental Table 4: Kras mutational profiling on select donor samples Supplemental Table 5: Antibodies used for multiplex immunofluoresence. Supplemental Table 6: Antibodies and RNAScope probe used for co-IF/ISH.

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ARTICLE ABSTRACT

The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis. Precursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression.

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    cancer

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