Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.

Ji Dong; Xinglong WU; Xin Zhou; Yuan Gao; Changliang Wang; Wendong Wang; Weiya HE; Jingyun LI; Wenjun Deng; Jiayu Liao; Xiaotian WU; Yongqu LU; Antony K Chen; Lu Wen; Wei FU; Fuchou Tang

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Spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium.

Author: Ji DONG ¹ ; Xinglong WU ² ; Xin ZHOU ¹ ; Yuan GAO ¹ ; Changliang WANG ³ ; Wendong WANG ¹ ; Weiya HE ³ ; Jingyun LI ¹ ; Wenjun DENG ³ ; Jiayu LIAO ³ ; Xiaotian WU ⁴ ; Yongqu LU ¹ ; Antony K CHEN ⁴ ; Lu WEN ¹ ; Wei FU ¹ ; Fuchou TANG ¹
Author Information

1. Biomedical Pioneering Innovation Center, Department of General Surgery, College of Life Sciences, Third Hospital, Peking University, Beijing 100871, China.
2. College of Animal Science and Technology, Hebei Agricultural University, Baoding 071001, China.
3. GMU-GIBH Joint School of Life Sciences, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou 510799, China.
4. Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: gastric corpus stem/progenitor cell; human gastric corpus; regulatory network; single-cell ATAC-seq; single-cell omics sequencing; spatial transcriptomics
MeSH: Humans; Epigenesis, Genetic; Gastric Mucosa/metabolism*; Chromatin/metabolism*; Stem Cells; Epithelium/metabolism*; Fatty Acid-Binding Proteins/metabolism*
From: Protein & Cell 2023;14(6):433-447
CountryChina
Language:English
Abstract: Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.