Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma

被引:37
作者
Chijimatsu, Ryota [1 ,2 ]
Kobayashi, Shogo [3 ]
Takeda, Yu [3 ]
Kitakaze, Masatoshi [3 ]
Tatekawa, Shotaro [4 ]
Arao, Yasuko [1 ]
Nakayama, Mika [1 ]
Tachibana, Naohiro [5 ]
Saito, Taku [5 ]
Ennishi, Daisuke [2 ]
Tomida, Shuta [2 ]
Sasaki, Kazuki [3 ]
Yamada, Daisaku [3 ]
Tomimaru, Yoshito [3 ]
Takahashi, Hidenori [3 ]
Okuzaki, Daisuke [6 ]
Motooka, Daisuke [6 ]
Ohshiro, Takahito [7 ]
Taniguchi, Masateru [7 ]
Suzuki, Yutaka [8 ]
Ogawa, Kazuhiko [4 ]
Mori, Masaki [3 ,9 ]
Doki, Yuichiro [3 ]
Eguchi, Hidetoshi [3 ]
Ishii, Hideshi [1 ]
机构
[1] Osaka Univ, Dept Med Data Sci, Ctr Med Innovat & Translat Res, Grad Sch Med, Yamadaoka 2-2, Suita, Osaka 5650871, Japan
[2] Okayama Univ Hosp, Ctr Comprehens Genom Med, Kita Ku, Shikata Cho, Okayama 7008558, Japan
[3] Osaka Univ, Dept Gastroenterol, Grad Sch Med, Yamadaoka 2-2, Suita, Osaka 5650871, Japan
[4] Osaka Univ, Dept Radiat Oncol, Grad Sch Med, Yamadaoka 2-2, Suita, Osaka 5650871, Japan
[5] Univ Tokyo, Dept Orthopaed Surg, Sect Sensory & Motor Syst Med, Sch Med,Bunkyo Ku, Tokyo 1138655, Japan
[6] Osaka Univ, Genome Informat Res Ctr, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan
[7] Osaka Univ, SANKEN Inst Sci & Ind Res, 8-1 Mihogaoka, Osaka, Ibaraki 5670047, Japan
[8] Univ Tokyo, Lab Syst Genom, Dept Computat Biol & Med Sdences, Grad Sch Frontier Sci, Kashiwa, Chiba 2728562, Japan
[9] Tokai Univ, Grad Sch Med, Isehara, Kanagawa 2591193, Japan
关键词
TO-MESENCHYMAL TRANSITION; DUCTAL ADENOCARCINOMA; SUBTYPES; CANCER; COMMUNICATION; EXPRESSION; INFERENCE;
D O I
10.1016/j.isci.2022.104659
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Single-cell RNA sequencing (scRNAseq) has been used to assess the intra-tumor heterogeneity and microenvironment of pancreatic ductal adenocarcinoma (PDAC). However, previous knowledge is not fully universalized. Here, we built a single cell atlas of PDAC from six datasets containing over 70 samples and >130,000 cells, and demonstrated its application to the reanalysis of the previous bulk transcriptomic cohorts and inferring cell-cell communications. The cell decomposition of bulk transcriptomics using scRNAseq data showed the cellular heterogeneity of PDAC; moreover, high levels of tumor cells and fibroblasts were indicative of poor-prognosis. Refined tumor subtypes signature indicated the tumor cell dynamics in intra-tumor and their specific regulatory network. We further identified functionally distinct tumor clusters that had close interaction with fibroblast subtypes via different signaling pathways dependent on subtypes. Our analysis provided a reference dataset for PDAC and showed its utility in research on the microenvironment of intra-tumor heterogeneity.
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页数:22
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共 74 条
[1]  
Aibar S, 2017, NAT METHODS, V14, P1083, DOI [10.1038/NMETH.4463, 10.1038/nmeth.4463]
[2]   Genomic analyses identify molecular subtypes of pancreatic cancer [J].
Bailey, Peter ;
Chang, David K. ;
Nones, Katia ;
Johns, Amber L. ;
Patch, Ann-Marie ;
Gingras, Marie-Claude ;
Miller, David K. ;
Christ, Angelika N. ;
Bruxner, Tim J. C. ;
Quinn, Michael C. ;
Nourse, Craig ;
Murtaugh, L. Charles ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Manning, Suzanne ;
Nourbakhsh, Ehsan ;
Wani, Shivangi ;
Fink, Lynn ;
Holmes, Oliver ;
Chin, Vencssa ;
Anderson, Matthew J. ;
Kazakoff, Stephen ;
Leonard, Conrad ;
Newell, Felicity ;
Waddell, Nick ;
Wood, Scott ;
Xu, Qinying ;
Wilson, Peter J. ;
Cloonan, Nicole ;
Kassahn, Karin S. ;
Taylor, Darrin ;
Quek, Kelly ;
Robertson, Alan ;
Pantano, Lorena ;
Mincarelli, Laura ;
Sanchez, Luis N. ;
Evers, Lisa ;
Wu, Jianmin ;
Pinese, Mark ;
Cowley, Mark J. ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chantrill, Lorraine A. ;
Mawson, Amanda ;
Humphris, Jeremy ;
Chou, Angela ;
Pajic, Marina ;
Scarlett, Christopher J. .
NATURE, 2016, 531 (7592) :47-+
[3]   Broadening the Impact of Immunotherapy to Pancreatic Cancer: Challenges and Opportunities [J].
Balachandran, Vinod P. ;
Beatty, Gregory L. ;
Dougan, Stephanie K. .
GASTROENTEROLOGY, 2019, 156 (07) :2056-2072
[4]   A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure [J].
Baron, Maayan ;
Veres, Adrian ;
Wolock, Samuel L. ;
Faust, Aubrey L. ;
Gaujoux, Renaud ;
Vetere, Amedeo ;
Ryu, Jennifer Hyoje ;
Wagner, Bridget K. ;
Shen-Orr, Shai S. ;
Klein, Allon M. ;
Melton, Douglas A. ;
Yanai, Itai .
CELL SYSTEMS, 2016, 3 (04) :346-+
[5]   NicheNet: modeling intercellular communication by linking ligands to target genes [J].
Browaeys, Robin ;
Saelens, Wouter ;
Saeys, Yvan .
NATURE METHODS, 2020, 17 (02) :159-+
[6]  
Brunton H., 2020, Cell Rep., V1, DOI [10.1016/j.xpro, DOI 10.1016/J.XPRO]
[7]   The role of lineage specifiers in pancreatic ductal adenocarcinoma [J].
Camolotto, Soledad A. ;
Belova, Veronika K. ;
Snyder, Eric L. .
JOURNAL OF GASTROINTESTINAL ONCOLOGY, 2018, 9 (06) :1005-1013
[8]   Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma [J].
Aguirre, Andrew J. ;
Hruban, Ralph H. ;
Raphael, Benjamin J. .
CANCER CELL, 2017, 32 (02) :185-+
[9]   Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer [J].
Carstens, Julienne L. ;
Yang, Sujuan ;
de Sampaio, Pedro Correa ;
Zheng, Xiaofeng ;
Barua, Souptik ;
McAndrews, Kathleen M. ;
Rao, Arvind ;
Burks, Jared K. ;
Rhim, Andrew D. ;
Kalluri, Raghu .
CELL REPORTS, 2021, 35 (02)
[10]   Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution [J].
Chan-Seng-Yue, Michelle ;
Kim, Jaeseung C. ;
Wilson, Gavin W. ;
Ng, Karen ;
Figueroa, Eugenia Flores ;
O'Kane, Grainne M. ;
Connor, Ashton A. ;
Denroche, Robert E. ;
Grant, Robert C. ;
McLeod, Jessica ;
Wilson, Julie M. ;
Jang, Gun Ho ;
Zhang, Amy ;
Liang, Sheng-Ben ;
Borgida, Ayelet ;
Chadwick, Dianne ;
Kalimuthu, Sangeetha ;
Lungu, Ilinca ;
Bartlett, John M. S. ;
Krzyzanowski, Paul M. ;
Sandhu, Vandana ;
Tiriac, Herve ;
Froeling, Fieke E. M. ;
Karasinska, Joanna M. ;
Topham, James T. ;
Renouf, Daniel J. ;
Schaeffer, David F. ;
Jones, Steven J. M. ;
Marra, Marco A. ;
Laskin, Janessa ;
Chetty, Runjan ;
Stein, Lincoln D. ;
Zogopoulos, George ;
Haibe-Kains, Benjamin ;
Campbell, Peter J. ;
Tuveson, David A. ;
Knox, Jennifer J. ;
Fischer, Sandra E. ;
Gallinger, Steven ;
Notta, Faiyaz .
NATURE GENETICS, 2020, 52 (02) :231-+