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Cited by 284

The DOI matches its Crossref record; 145 of the 145 references it cites were found in a registry or an index.

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

Open access
Cui Zhou, Daniel, 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, Naser Al Deen, Nataly, Baer, John M., 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·2022·Nature Genetics
DOI 10.1038/s41588-022-01157-1
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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 transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease.

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Authors
Cui Zhou, D., Jayasinghe, R. G., Chen, S., Herndon, J. M., Iglesia, M. D., Navale, P., Wendl, M. C., Caravan, W., Sato, K., Storrs, E., Mo, C.-K., Liu, J., Southard-Smith, A. N., Wu, Y., Naser Al Deen, N., Baer, J. M., Fulton, R. S., Wyczalkowski, M. A., Liu, R., Fronick, C. C., Fulton, L. A., Shinkle, A., Thammavong, L., Zhu, H., Sun, H., Wang, L.-B., Li, Y., Zuo, C., McMichael, J. F., Davies, S. R., Appelbaum, E. L., Robbins, K. J., Chasnoff, S. E., Yang, X., Reeb, A. N., Oh, C., Serasanambati, M., Lal, P., Varghese, R., Mashl, J. R., Ponce, J., Terekhanova, N. V., Yao, L., Wang, F., Chen, L., Schnaubelt, M., Lu, R. J.-H., Schwarz, J. K., Puram, S. V., Kim, A. H., Song, S.-K., Shoghi, K. I., Lau, K. S., Ju, T., Chen, K., Chatterjee, D., Hawkins, W. G., Zhang, H., Achilefu, S., Chheda, M. G., Oh, S. T., Gillanders, W. E., Chen, F., DeNardo, D. G., Fields, R. C., & Ding, L.
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2022-08-22
Volume
54
Issue
9
Pages
1390-1405
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/s41588-022-01157-1
OpenAlex
W4292641742
Cited by
284
References
145
FWCI
20.57
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer. https://app.cochat.ai/papers/10.1038/s41588-022-01157-1
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Cui Zhou, D., Jayasinghe, R. G., Chen, S., Herndon, J. M., Iglesia, M. D., Navale, P., Wendl, M. C., Caravan, W., Sato, K., Storrs, E., Mo, C.-K., Liu, J., Southard-Smith, A. N., Wu, Y., Naser Al Deen, N., Baer, J. M., Fulton, R. S., Wyczalkowski, M. A., Liu, R., . . . Ding, L. (2022). Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer. Nature Genetics. https://doi.org/10.1038/s41588-022-01157-1

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.