Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer

Zhou, Daniel Cui; Jayasinghe, Reyka G.; Chen, Siqi; Herndon, John M.; Iglesia, Michael D.; Navale, Pooja; Wendl, Michael C.; Caravan, Wagma; Sato, Kazuhito; Storrs, Erik; Mo, Chia-Kuei; Liu, Jingxian; Southard-Smith, Austin N.; Wu, Yige; Deen, Nataly Naser Al; Baer, John; Fulton, Robert S.; Wyczalkowski, Matthew A.; Liu, Ruiyang; Fronick, Catrina C.; Fulton, Lucinda A.; Shinkle, Andrew; Thammavong, Lisa; Zhu, Houxiang; Sun, Hua; Wang, Liang-Bo; Li, Yize; Zuo, Chong; McMichael, Joshua F.; Davies, Sherri R.; Appelbaum, Elizabeth L.; Robbins, Keenan J.; Chasnoff, Sara E.; Yang, Xiaolu; Reeb, Ashley N.; Oh, Clara; Serasanambati, Mamatha; Lal, Preet; Varghese, Rajees; Mashl, Jay R.; Ponce, Jennifer; Terekhanova, Nadezhda V.; Yao, Lijun; Wang, Fang; Chen, Lijun; Schnaubelt, Michael; Lu, Rita Jui-Hsien; Schwarz, Julie K.; Puram, Sidharth V.; Kim, Albert H.; Song, Sheng‐Kwei; Shoghi, Kooresh I.; Lau, Ken S.; Ju, Tao; Chen, Ken; Chatterjee, Deyali; Hawkins, William G.; Zhang, Hui; Achilefu, Samuel; Chheda, Milan G.; Oh, Stephen T.; Gillanders, William E.; Chen, Feng; DeNardo, David G.; Fields, Ryan C.; Ding, Li

doi:10.1038/s41588-022-01157-1

articleNature GeneticsAug 22, 2022HYBRID OA

Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer

DCDaniel Cui Zhou RGReyka G. Jayasinghe SCSiqi Chen JMJohn M. Herndon MDMichael D. Iglesia

James S. McDonnell Foundation · Washington University in St. Louis · +5 more institutions

PubMed

Indexed incrossrefpubmed

Abstract

Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and…

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282

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FWCI: 27.87
Percentile: 100%
References: 118

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66

Topics & keywords

Topics

Keywords

Biology
KRAS
Cancer research
Pancreatic Intraepithelial Neoplasia
Pancreatic cancer
Transcriptome
Tumor microenvironment
Transdifferentiation

UN Sustainable Development Goals

Good health and well-being

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