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

被引:4
作者
Dong, Ji [1 ,2 ,8 ]
Wu, Xinglong [3 ]
Zhou, Xin [1 ,6 ]
Gao, Yuan [1 ,7 ]
Wang, Changliang [2 ]
Wang, Wendong [1 ]
He, Weiya [2 ,8 ]
Li, Jingyun [1 ]
Deng, Wenjun [2 ]
Liao, Jiayu [2 ]
Wu, Xiaotian [4 ]
Lu, Yongqu [1 ]
Chen, Antony K. [4 ]
Wen, Lu [1 ,5 ]
Fu, Wei [1 ,6 ]
Tang, Fuchou [1 ,5 ,7 ]
机构
[1] Third Hosp Peking Univ, Coll Life Sci, Biomed Pioneering Innovat Ctr, Dept Gen Surg, Beijing 100871, Peoples R China
[2] Guangzhou Med Univ, GMU GIBH Joint Sch Life Sci, Guangzhou Lab, Guangzhou 510799, Peoples R China
[3] Hebei Agr Univ, Coll Anim Sci & Technol, Baoding 071001, Peoples R China
[4] Peking Univ, Coll Engn, Dept Biomed Engn, Beijing 100871, Peoples R China
[5] Beijing Adv Innovat Ctr Genom ICG, Key Lab Cell Proliferat & Differentiat, Minist Educ, Beijing 100871, Peoples R China
[6] Peking Univ Third Hosp, Canc Ctr, Beijing 100191, Peoples R China
[7] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China
[8] Bioland Lab, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou 510320, Peoples R China
基金
中国国家自然科学基金;
关键词
human gastric corpus; gastric corpus stem; progenitor cell; single-cell omics sequencing; single-cell ATAC-seq; spatial transcriptomics; regulatory network; STEM-CELLS; STOMACH; IDENTIFICATION; ACCESSIBILITY; PROGENITOR; CANCER;
D O I
10.1093/procel/pwac059
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:433 / 447
页数:15
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