类器官揭示BMP信号在胃上皮细胞分化中的关键作用。

IF 4 Q2 CELL & TISSUE ENGINEERING
Fan Hong, Xiaodan Wang, Nanshan Zhong, Ze Zhang, Shibo Lin, Mengxian Zhang, Haonan Li, Yuan Liu, Yalong Wang, Lianzheng Zhao, Xiao Yang, Hongwen Zhou, Hui Liang, Ye-Guang Chen
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引用次数: 0

摘要

成体胃干细胞向特定上皮细胞类型的有效分化对胃内稳态至关重要。虽然人们已经认识到生态位在胃上皮细胞分化中起着关键作用,但相关的分子因素和潜在的调节机制仍然知之甚少。在本研究中,我们结合单细胞RNA测序获得的小生境细胞知识和信号通路的操纵,在小鼠和人胃类器官中实现了多种胃上皮细胞类型的有效分化。这些体外分化的细胞显示出与胃组织相似的基因表达谱。具体来说,BMP4信号传导刺激窝细胞和壁细胞分化。此外,BMP4和EGF信号共同促进窝细胞分化,而抑制TGF-β和BMP4信号则促进主细胞分化。我们证明Zbtb7b是一种控制坑细胞分化的新型调节剂。此外,BMP4与小分子异恶唑9一起促进壁和肠内分泌细胞分化。我们的数据还揭示了小鼠和人对顶细胞和主细胞分化的不同要求。总之,我们的研究结果提供了对胃上皮细胞分化机制的深入了解,揭示了小鼠和人类胃上皮细胞分化的异同,为未来研究胃类器官和潜在的临床应用奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The critical role of BMP signaling in gastric epithelial cell differentiation revealed by organoids.

The efficient differentiation of adult gastric stem cells into specific epithelial cell types is crucial for gastric homeostasis. Although it is well appreciated that the niche plays a critical role in gastric epithelium cell differentiation, the relevant molecular factors and the underlying regulatory mechanisms remain poorly understood. In this study, by combining the knowledge of the niche cells obtained from single-cell RNA sequencing and manipulation of signaling pathways, we achieved effective differentiation of various gastric epithelial cell types in mouse and human gastric organoids. These in vitro differentiated cells showed a similar gene expression profile to those in gastric tissues. Specifically, BMP4 signaling stimulates pit cell and parietal cell differentiation. Furthermore, BMP4 and EGF signaling cooperate to enhance pit cell differentiation, whereas inhibition of TGF-β and BMP4 signaling promotes chief cell differentiation. We demonstrated that Zbtb7b is a novel regulator controlling pit cell differentiation. In addition, BMP4, together with the small molecule Isoxazole 9, promotes parietal and enteroendocrine cell differentiation. Our data also revealed the different requirements of parietal and chief cell differentiation between mouse and human. Together, our findings provide a mechanistic insight into gastric epithelial cell differentiation and uncover its similarities and differences between mouse and human, laying a foundation for future investigation and potential clinical use of gastric organoids.

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来源期刊
Cell Regeneration
Cell Regeneration Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
5.80
自引率
0.00%
发文量
42
审稿时长
35 days
期刊介绍: Cell Regeneration aims to provide a worldwide platform for researches on stem cells and regenerative biology to develop basic science and to foster its clinical translation in medicine. Cell Regeneration welcomes reports on novel discoveries, theories, methods, technologies, and products in the field of stem cells and regenerative research, the journal is interested, but not limited to the following topics: ◎ Embryonic stem cells ◎ Induced pluripotent stem cells ◎ Tissue-specific stem cells ◎ Tissue or organ regeneration ◎ Methodology ◎ Biomaterials and regeneration ◎ Clinical translation or application in medicine
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