对Wnt信号激活的单细胞反应揭示了Wnt目标基因表达的解
Simon Söderholm1, Amaia Jauregi-Miguel1, Pierfrancesco Pagella1
1Wallenberg Centre for Molecular Medicine, Linköping University, Linköping, Sweden; Department of Biomedical and Clinical Sciences, Division of Molecular Medicine and Virology, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Experimental cell research
|June 4, 2023
概括
Wnt信号激活基因,但单细胞研究显示出不同的反应. 并非所有细胞都能同样激活Wnt目标基因,这表明,除了简单的途径刺激之外,还存在复杂的调节.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 干细胞生物学 干细胞生物学
背景情况:
- 涉及β-catenin和TCF/LEF因子的Wnt信号传递对于基因调节至关重要.
- 通常认为Wnt目标基因在途径刺激时集体激活.
- 观察到的非重叠的基因表达模式挑战了这种集体激活模型.
研究的目的:
- 在单细胞分辨率下调查Wnt目标基因表达异质性.
- 了解人类胚胎干细胞中Wnt通路激活的动态.
- 确定在单细胞中的可变转录输出背后的机制.
主要方法:
- 在Wnt通路刺激后,人类胚胎干细胞的单细胞转录组学.
- 对基因表达动态的分析,包括多能性,Wnt标和中皮标记物.
- 在HEK293T细胞,小鼠前肢发育和人类结直肠癌中进行比较分析.
主要成果:
- 人类胚胎干细胞表现出Wnt目标基因激活的连续性,从强响应到弱响应.
- 高AXIN2表达不总是与其他Wnt目标的高水平相关.
- 在其他细胞类型和环境中也观察到未合的Wnt目标基因表达.
结论:
- 在单细胞水平上,Wnt/β-catenin介导的转录输出是异质的.
- 假设集体Wnt目标基因激活并不普遍适用.
- 需要进一步的研究来阐明驱动这种观察到的异质性的机制.
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