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Updated: Jul 3, 2025

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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
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确定一个核心的转录程序,驱动人类中细胞到上皮细胞的过渡
John-Poul Ng-Blichfeldt1, Benjamin J Stewart2, Menna R Clatworthy3
1MRC-Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Developmental cell
|February 10, 2024
概括
人类脏器官表明,PAX8启动介质细胞到上皮细胞的转换 (MET) 来促进脏的发育. 减弱的Wnt/β-catenin信号使HNF1B和TEAD因子能够完成这一关键的上皮转化.
科学领域:
- 发育生物学 发展生物学
- 尼弗洛基尼斯发生.
- 皮质生物学 皮质生物学
背景情况:
- 脏上皮质由中细胞的祖先通过中细胞到上皮细胞的过渡 (MET) 形成.
- 在人类脏发育过程中,对脏MET的转录控制尚不清楚.
- 人类诱导的多能干细胞衍生脏器官模型人类产.
研究的目的:
- 研究控制人类脏发育中的脏MET的机制.
- 确定关键的转录因子和参与脏MET的信号通路.
- 了解细胞命运承诺和人类脏的形态发生之间的相互作用.
主要方法:
- 使用人类iPSC衍生的器官.
- 进行了多原子分析 (snRNA-seq 和 ATAC-seq).
- 在基因功能研究中使用CRISPR干扰.
主要成果:
- 在脏MET期间确定了动态基因表达和染色质可访问性变化.
- PAX8 (配对框8) 对于在人类器官中启动MET至关重要,激活细胞粘附程序.
- 对于HNF1B (肝细胞核因子1-β) 和TEAD (TEA-域) 因子来说,需要Wnt/β-catenin信号衰减来推动MET完成.
结论:
- 发现PAX8,HNF1B和TEAD在人类脏MET中的关键作用.
- 阐明了Wnt/β-catenin信号传递,命运承诺和上皮形态发生之间的相互作用.
- 提供了对发育性病和管损伤修复机制的见解.
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