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

doi:10.1016/j.celrep.2023.113236

Stomach encyclopedia: Combined single-cell and spatial transcriptomics reveal cell diversity and homeostatic regulation of human stomach

Cell Rep. 2023 Oct 31;42(10):113236. doi: 10.1016/j.celrep.2023.113236. Epub 2023 Oct 17.

Authors

Affiliations

¹ Department of Preventive Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku 1130033, Tokyo, Japan.
² 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.
³ Dpartment of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-ku 1130033, Tokyo, Japan.
⁴ Department of Gastrointestinal Surgery, Graduate School of Medicine, The University of Tokyo, 7-3-1, Hongo, Bunkyo-kyu 1130033, Tokyo, Japan.
⁵ 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. Electronic address: ishum-prm@m.u-tokyo.ac.jp.

PMID: 37819756
DOI: 10.1016/j.celrep.2023.113236

Abstract

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.

Keywords: CP: Genomics; intestinal metaplasia; scRNA-seq; spatial transcriptome; stem cell; stomach.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinogenesis
Gene Expression Profiling
Humans
Sequence Analysis, RNA
Single-Cell Analysis
Stomach Neoplasms* / genetics
Transcriptome* / genetics