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 SuzukiKazuhiko Ogawa, Masaki Mori, Yuichiro Doki, Hidetoshi Eguchi, Hideshi Ishii

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number104659
JournaliScience
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 19 2022

Keywords

  • Cancer
  • Cancer systems biology
  • Transcriptomics

ASJC Scopus subject areas

  • General

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