@article{fd1b6e1322b84ca28a277748b6f0d2eb,
title = "Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma",
abstract = "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.",
keywords = "Cancer, Cancer systems biology, Transcriptomics",
author = "Ryota Chijimatsu and Shogo Kobayashi and Yu Takeda and Masatoshi Kitakaze and Shotaro Tatekawa and Yasuko Arao and Mika Nakayama and Naohiro Tachibana and Taku Saito and Daisuke Ennishi and Shuta Tomida and Kazuki Sasaki and Daisaku Yamada and Yoshito Tomimaru and Hidenori Takahashi and Daisuke Okuzaki and Daisuke Motooka and Takahito Ohshiro and Masateru Taniguchi and Yutaka Suzuki and Kazuhiko Ogawa and Masaki Mori and Yuichiro Doki and Hidetoshi Eguchi and Hideshi Ishii",
note = "Funding Information: We thank Ms. Otsuka, C. and Ms. Hamano, Y., for fruitful discussion and excellent support of preparation of our research manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology ( 15H05791 [M.M. and H.I.]; 20K18053 [R.C.]; 20H00541 [H.I.]; 21K19526 [H.I.]) and JSPS KAKENHI Grant Number 16H06279 (PAGS) [Y.S. and H.I.]. Partial support was received from Takeda Medical Research Foundation [R.C.], Kowa Life Science Foundation [R.C.], Princess Takamatsu Cancer Research Fund [H.I.], Senshin Medical Research Foundation [H.I.], and Mitsubishi Foundation [H.I.]. Funding Information: We thank Ms. Otsuka, C. and Ms. Hamano, Y. for fruitful discussion and excellent support of preparation of our research manuscript. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (15H05791 [M.M. and H.I.]; 20K18053 [R.C.]; 20H00541 [H.I.]; 21K19526 [H.I.]) and JSPS KAKENHI Grant Number 16H06279 (PAGS) [Y.S. and H.I.]. Partial support was received from Takeda Medical Research Foundation [R.C.], Kowa Life Science Foundation [R.C.], Princess Takamatsu Cancer Research Fund [H.I.], Senshin Medical Research Foundation [H.I.], and Mitsubishi Foundation [H.I.]. Conception, R.C. H.E. and H.I.; Design of the Work, R.C. S.K. D.Y. H.T. T.O. M.T. K.M. M.M. Y.D. H.E. and H.I.; Acquisition and Analysis, C.R. S.K. Y.T. M.K. Y.A. M.N. N.T. K.S. D.Y. Y.T. D.O. D.M. Y.S. and H.I.; Interpretation of Data, R.C. S.K. Y.T. M.K. T.S. D.E. S.T. D.Y. H.T. H.E. and H.I.; Manuscript Writing and Revision, R.C. and H.I.; Final Approval of the Manuscript, All Authors. Agreement to own Contributions, All Authors. Partial institutional endowments were received from Taiho Pharmaceutical Co. Ltd. (Tokyo, Japan), Hirotsu Bio Science Inc. (Tokyo, Japan), Kinshu-kai Medical Corporation (Osaka, Japan), Kyowa-kai Medical Corporation (Osaka, Japan), IDEA Consultants Inc. (Tokyo, Japan), and Unitech Co. Ltd. (Chiba, Japan). Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = aug,
day = "19",
doi = "10.1016/j.isci.2022.104659",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "8",
}