ISSN: 1001-0602
EISSN: 1748-7838
2012 impact factor 10.526*
(Thomson Reuters, 2013)
Free Sample Issue
 

VOLUME 29 ISSUE 9(9,2019): 725-738

 

Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma

 

Junya Peng1, Bao-Fa Sun 2,3,4, Chuan-Yuan Chen 2,3, Jia-Yi Zhou 2,3, Yu-Sheng Chen 2,3, Hao Chen 5, Lulu Liu1, Dan Huang1, Jialin Jiang5,Guan-Shen Cui 2,3, Ying Yang 2,3,4, Wenze Wang6, Dan Guo 1,7, Menghua Dai5, Junchao Guo5, Taiping Zhang5, Quan Liao5, Yi Liu8,Yong-Liang Zhao 2,3,4, Da-Li Han 2,3,4, Yupei Zhao 5,8, Yun-Gui Yang 2,3,4 and Wenming Wu5

 

1 Department of Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China; 2CAS Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, College of Future Technology, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China; 3University of Chinese Academy of Sciences, 100049 Beijing, China; 4Institute of Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China; 5Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China; 6Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China; 7Clinical Biobank, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, 100730 Beijing, China and 8Tsinghua University-Peking University Joint Center for Life Sciences, School of Medicine, Tsinghua University, 100084 Beijing, China

Correspondence:Yupei Zhao (zhao8028@263.net) or Yun-Gui Yang (ygyang@big.ac.cn) or Wenming Wu (doctorwuu@126.com)
These authors contributed equally: Junya Peng, Bao-Fa Sun, Chuan-Yuan Chen, Jia-Yi Zhou, Yu-Sheng Chen        

 

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer featured with high intra-tumoral heterogeneity and poor prognosis. To comprehensively delineate the PDAC intra-tumoral heterogeneity and the underlying mechanism for PDAC progression, we employed single-cell RNA-seq (scRNA-seq) to acquire the transcriptomic atlas of 57,530 individual pancreatic cells from primary PDAC tumors and control pancreases, and identified diverse malignant and stromal cell types, including two ductal subtypes with abnormal and malignant gene expression profiles respectively, in PDAC. We found that the heterogenous malignant subtype was composed of several subpopulations with differential proliferative and migratory potentials. Cell trajectory analysis revealed that components of multiple tumor-related pathways and transcription factors (TFs) were differentially expressed along PDAC progression. Furthermore, we found a subset of ductal cells with unique proliferative features were associated with an inactivation state in tumor-infiltrating T cells, providing novel markers for the prediction of antitumor immune response. Together, our findings provide a valuable resource for deciphering the intra-tumoral heterogeneity in PDAC and uncover a connection between tumor intrinsic transcriptional state and T cell activation, suggesting potential biomarkers for anticancer treatment such as targeted therapy and immunotherapy.

 

https://doi.org/10.1038/s41422-019-0195-y

 
 
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