Stomach encyclopedia: Combined single-cell and spatial transcriptomics reveal cell diversity and homeostatic regulation of human stomach
Ayumu Tsubosaka,
Daisuke Komura,
Miwako Kakiuchi,
Hiroto Katoh,
Takumi Onoyama,
Asami Yamamoto,
Hiroyuki Abe,
Yasuyuki Seto,
Tetsuo Ushiku,
Shumpei Ishikawa
Affiliations
Ayumu Tsubosaka
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Daisuke Komura
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Miwako Kakiuchi
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Hiroto Katoh
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Takumi Onoyama
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan; Division of Gastroenterology and Nephrology, Department of Multidisciplinary Internal Medicine, School of Medicine, Faculty of Medicine, Tottori University, 36-1, Nishicho, Yonago 683-8504, Tottori, Japan
Asami Yamamoto
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Hiroyuki Abe
Dpartment of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Yasuyuki Seto
Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-kyu 1130033, Tokyo, Japan
Tetsuo Ushiku
Dpartment of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku 1130033, Tokyo, Japan
Shumpei Ishikawa
Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan; Division of Pathology, National Cancer Center Exploratory Oncology Research & Clinical Trial Center, 6-5-1, Kashiwanoha, Kashiwa 277-8577, Chiba, Japan; Corresponding author
Summary: The stomach is an important digestive organ with various biological functions. However, because of the complexity of its cellular and glandular composition, its precise cellular biology has yet to be elucidated. In this study, we conducted single-cell RNA sequencing (scRNA-seq) and subcellular-level spatial transcriptomics analysis of the human stomach and constructed the largest dataset to date: a stomach encyclopedia. This dataset consists of approximately 380,000 cells from scRNA-seq and the spatial transcriptome, enabling integrated analyses of transcriptional and spatial information of gastric and metaplastic cells. This analysis identified LEFTY1 as an uncharacterized stem cell marker, which was confirmed through lineage tracing analysis. A wide variety of cell-cell interactions between epithelial and stromal cells, including PDGFRA+BMP4+WNT5A+ fibroblasts, was highlighted in the developmental switch of intestinal metaplasia. Our extensive dataset will function as a fundamental resource in investigations of the stomach, including studies of development, aging, and carcinogenesis.
