独特的SOX9单分子动力学标志着成人的分化和肠道器官中的胎儿类重编程状态
Nike Walther1, Sathvik Anantakrishnan2, Gina M Dailey3
1Department of Molecular and Cell Biology, Li Ka Shing Center for Biomedical and Health Sciences, California Institute for Regenerative Medicine (CIRM) Center of Excellence, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Genetics, University of Bayreuth, 95440 Bayreuth, Germany.
单分子追踪揭示了SOX9的动态如何在肠道分化过程中发生变化. 过度表达SOX9可以使成年细胞恢复到类似胎儿的状态,影响组织身份.
科学领域:
- 分子生物学分子生物学
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
背景情况:
- 转录因子 (TFs) 在细胞分化和发育过程中调节基因表达.
- 在细胞状态转换中TF生物物理性质和丰度的确切作用尚未完全理解.
研究的目的:
- 在肠道分化过程中调查性别决定区域Y盒子9 (SOX9) 生物物理性质的动态调节.
- 探索SOX9过度表达对肠道有机体形态,增殖和身份的影响.
主要方法:
- 自动活细胞单分子追踪 (SMT) 用于肠道有机体模型.
- 在分化过程中和SOX9过度表达时,分析了SOX9的分子动力学,DNA结合和自我相互作用.
主要成果:
- 在分化过程中观察到不运动的SOX9分子 (从~48%降至~38%) 的比例下降,独立于表达水平和依赖于DNA结合.
- 长期的SOX9过度表达诱导了从芽到球状形态的转变,增加了增殖,并减少了肠道基因表达特征.
- 在重编程的胎儿状状态下,较高比例的SOX9分子 (~61%) 表现出部分自我相互作用和DNA结合.
结论:
- 在成年人肠道分化过程中,SOX9单分子动力学是取决于上下文的,并且在过度表达时可以驱动胎儿类的逆转.
- 这项研究强调了自动活细胞SMT在揭示基础组织表型的分子机制方面的实用性.
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