Numerous recent studies using single cell RNA sequencing and spatial transcriptomics have shown the vast cell heterogeneity, including epithelial, immune, and stromal cells, present in the normal human stomach and at different stages of gastric carcinogenesis. Fibroblasts within the metaplastic and dysplastic mucosal stroma represent key contributors to the carcinogenic microenvironment in the stomach. The heterogeneity of fibroblast populations is present in the normal stomach, but plasticity within these populations underlies their alterations in association with both metaplasia and dysplasia. In this review, we summarize and discuss efforts over the past several years to study the fibroblast components in human stomach from normal to metaplasia, dysplasia, and cancer. In the stomach, myofibroblast populations increase during late phase carcinogenesis and are a source of matrix proteins. PDGFRA-expressing telocyte-like cells are present in normal stomach and expand during metaplasia and dysplasia in close proximity with epithelial lineages, likely providing support for both normal and metaplastic progenitor niches. The alterations in fibroblast transcriptional signatures across the stomach carcinogenesis process indicate that fibroblast populations are likely as plastic as epithelial populations during the evolution of carcinogenesis.

中文翻译：

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胃癌发生过程中的成纤维细胞景观

最近使用单细胞 RNA 测序和空间转录组学的大量研究表明，正常人胃和胃癌发生的不同阶段存在巨大的细胞异质性，包括上皮细胞、免疫细胞和基质细胞。化生和发育不良粘膜基质内的成纤维细胞是胃致癌微环境的关键贡献者。正常胃中存在成纤维细胞群体的异质性，但这些群体内的可塑性是其与化生和发育不良相关的改变的基础。在这篇综述中，我们总结并讨论了过去几年研究人胃成纤维细胞成分（从正常到化生、不典型增生和癌症）的努力。在胃中，肌成纤维细胞群在晚期癌发生过程中增加，并且是基质蛋白的来源。表达 PDGFRA 的端细胞样细胞存在于正常胃中，并在化生和不典型增生期间扩张，与上皮谱系非常接近，可能为正常和化生祖细胞生态位提供支持。胃癌发生过程中成纤维细胞转录特征的变化表明，在癌发生的进化过程中，成纤维细胞群体可能与上皮细胞群体一样具有可塑性。