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

Ryota Chijimatsu; Shogo Kobayashi; Yu Takeda; Masatoshi Kitakaze; Shotaro Tatekawa; Yasuko Arao; Mika Nakayama; Naohiro Tachibana; Taku Saito; Daisuke Ennishi; Shuta Tomida; Kazuki Sasaki; Daisaku Yamada; Yoshito Tomimaru; Hidenori Takahashi; Daisuke Okuzaki; Daisuke Motooka; Takahito Ohshiro; Masateru Taniguchi; Yutaka Suzuki; Kazuhiko Ogawa; Masaki Mori; Yuichiro Doki; Hidetoshi Eguchi; Hideshi Ishii

doi:10.1016/j.isci.2022.104659

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

iScience. 2022 Jun 22;25(8):104659. doi: 10.1016/j.isci.2022.104659. eCollection 2022 Aug 19.

Authors

Ryota Chijimatsu^{1

2}, Shogo Kobayashi³, Yu Takeda³, Masatoshi Kitakaze³, Shotaro Tatekawa⁴, Yasuko Arao¹, Mika Nakayama¹, Naohiro Tachibana⁵, Taku Saito⁵, Daisuke Ennishi², Shuta Tomida², Kazuki Sasaki³, Daisaku Yamada³, Yoshito Tomimaru³, Hidenori Takahashi³, Daisuke Okuzaki⁶, Daisuke Motooka⁶, Takahito Ohshiro⁷, Masateru Taniguchi⁷, Yutaka Suzuki⁸, Kazuhiko Ogawa⁴, Masaki Mori^{3

9}, Yuichiro Doki³, Hidetoshi Eguchi³, Hideshi Ishii¹

Affiliations

¹ Department of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
² Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
³ Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
⁴ Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
⁵ Department of Orthopaedic Surgery, Section of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
⁶ Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
⁷ SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047, Japan.
⁸ Laboratory of Systems Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwanoha, Kashiwa-shi, Chiba 272-8562, Japan.
⁹ Tokai University Graduate School of Medicine, Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

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.