Cellular heterogeneity during mouse pancreatic ductal adenocarcinoma progression at single-cell resolution

• DOI: 10.1172/jci.insight.129212
• Publication Date: 2019-07-23T16:02:27Z
• Authors: Abdel Nasser Hosein; Huocong Huang; Zhaoning Wang; Kamalpreet Parmar; Wenting Du; Jonathan Huang; Anirban Maitra; Eric Olson; Udit Verma; Rolf A. Brekken
• Keywords: Tumor progression; Tumour heterogeneity; Epigenome; Cancer-Associated Fibroblasts

Pancreatic ductal adenocarcinoma (PDA) is a major cause of cancer-related death with limited therapeutic options available. This highlights the need for improved understanding biology PDA progression, highly complex and dynamic process featuring changes in cancer cells stromal cells. A comprehensive characterization cell heterogeneity during disease progression lacking. In this study, we aimed to profile populations understand their phenotypic progression. To that end, employed single-cell RNA sequencing technology agnostically different stages genetically engineered mouse models. Our data indicate an epithelial-to-mesenchymal transition accompanies tumor addition distinct macrophages increasing inflammatory features. We also noted existence three molecular subtypes fibroblasts normal pancreas, which ultimately gave rise two advanced PDA, supporting recent reports on intratumoral fibroblast heterogeneity. suggest may be dynamically regulated by epigenetic mechanisms. study systematically describes landscape cellular has potential act as resource development strategies against specific disease.