iScience (Aug 2022)
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
Affiliations
- Ryota Chijimatsu
- 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; Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan
- Shogo Kobayashi
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Yu Takeda
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Masatoshi Kitakaze
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Shotaro Tatekawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Yasuko Arao
- 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
- Mika Nakayama
- 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
- Naohiro Tachibana
- 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
- Taku Saito
- 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
- Daisuke Ennishi
- Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan
- Shuta Tomida
- Center for Comprehensive Genomic Medicine, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama 700-8558, Japan
- Kazuki Sasaki
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Daisaku Yamada
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Yoshito Tomimaru
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Hidenori Takahashi
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Daisuke Okuzaki
- Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Daisuke Motooka
- Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
- Takahito Ohshiro
- SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047, Japan
- Masateru Taniguchi
- SANKEN (The Institute of Scientific and Industrial Research), Osaka University, 8-1 Mihogaoka, Osaka, Ibaraki 567-0047, Japan
- Yutaka Suzuki
- 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
- Kazuhiko Ogawa
- Department of Radiation Oncology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Masaki Mori
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan; Tokai University Graduate School of Medicine, Shimokasuya, Isehara, Kanagawa 259-1193, Japan
- Yuichiro Doki
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan
- Hidetoshi Eguchi
- Department of Gastroenterology, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan; Corresponding author
- Hideshi Ishii
- 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; Corresponding author
- Journal volume & issue
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Vol. 25,
no. 8
p. 104659
Abstract
Summary: 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.