Supplementary Figures Part 1 from Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions

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

doi:10.1158/2159-8290.22893206.v1

cd-23-0013_supplementary_figures_part_1_suppsf1.pdf (39.12 MB)

Supplementary Figures Part 1 from Analysis of Donor Pancreata Defines the Transcriptomic Signature and Microenvironment of Early Neoplastic Lesions

journal contribution

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

Supplementary Figures 1-10 and associated legends

History

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.