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.

中文翻译：

---

人胃体上皮的空间解析表达景观和基因调控网络。

人类胃体上皮的分子知识仍然不完整。在这里，通过使用单细胞 RNA 测序 (scRNA-seq)、空间转录组学和单细胞转座酶可及染色质测序 (scATAC-seq) 技术进行综合分析，我们揭示了空间分辨的表达景观和基因调控网络人胃体上皮。具体来说，我们在人胃体峡部鉴定了干细胞/祖细胞群，其中 EGF 和 WNT 信号通路被激活。同时，LGR4而非LGR5负责WNT信号通路的激活。重要的是，FABP5 和 NME1 被鉴定和验证对于正常胃干/祖细胞和胃癌细胞都至关重要。最后，我们在染色质状态水平上探索了胃体上皮关键基因的表观遗传调控，并鉴定了几种重要的细胞类型特异性转录因子。总之，我们的工作为系统地了解体内人胃体上皮的细胞多样性和稳态提供了新的见解。