2023 Fiscal Year Final Research Report

Discovery of glycan markers of pancreatic cancer stem cells by single-cell glycomics

Research Project

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Project/Area Number	22K19471
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 50:Oncology and related fields
Research Institution	National Institute of Advanced Industrial Science and Technology
Principal Investigator	Tateno Hiroaki 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (30450670)
Co-Investigator(Kenkyū-buntansha)	下村治筑波大学, 医学医療系, 講師 (60808070)
Project Period (FY)	2022-06-30 – 2024-03-31
Keywords	シングルセルグライコミクス / 膵癌 / 糖鎖マーカー
Outline of Final Research Achievements	By introducing droplet technology into scGR-seq, we constructed a technology for simultaneous analysis of 10,000 single cells and published a paper (Keisham et al. Small Methods 2024). We then analyzed pancreatic cancer cell lines and normal pancreatic duct cells, and compared the obtained data with those obtained by flow cytometry. The results showed that the data obtained by scGR-seq correlated well with those obtained by flow cytometry. The constructed droplet scGR-seq was used to analyze pancreatic cancer organoids and pancreatic cancer patient samples (n=6). Individual cell type classification was performed, and glycan profiles were obtained for each cell type. The changes in glycan profiles of pancreatic cancer subtypes during the transition from Basal to Classical were analyzed. In addition, we obtained information on the expression of glycogenes and human lectin receptor genes in each cell type.
Free Research Field	糖鎖生物学
Academic Significance and Societal Importance of the Research Achievements	膵癌の５年生存率は未だ１０％未満であり、新たな治療診断技術の開発が世界中で切望されている。本研究ではまずドロップレット技術を導入することで、１細胞ごとの糖鎖と遺伝子の発現情報、１万個分を一斉取得するための技術、ドロップレット型scGR-seq開発した。そして本技術を用いて膵癌患者腫瘍組織を解析することで、膵癌患者腫瘍組織中に存在する癌サブタイプ（Basal、Interemediate、Classical）、間質細胞、免疫細胞などの糖鎖プロファイルを一斉取得した。得られたデータを用いることで、膵癌の新たな創薬標的の同定が可能となり、標的医薬品や早期診断技術の開発への展開が期待できる。