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The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Generation of Dispersed Presomitic Mesoderm Cell Cultures for Imaging of the Zebrafish Segmentation Clock in Single Cells
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用多能干细胞总结人类细分时钟

Mitsuhiro Matsuda1,2, Yoshihiro Yamanaka3,4, Maya Uemura3,5

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研究人员使用诱导的多能干细胞建模了人类分片钟, 揭示了它的五小时周期和基因振荡. 这项研究提供了关于轴骨发育和相关疾病的见解.

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科学领域:

  • 发育生物学
  • 干细胞生物学
  • 遗传学

背景情况:

  • 多能干细胞是研究胚胎形成和器官形成的宝贵工具.
  • 现有的体外模型缺乏复杂性,无法完全复制人类中皮层的发育和模式.
  • 需要一个强大的实验系统来模拟人体体生殖和细分时钟.

研究的目的:

  • 使用诱导多能干细胞 (iPSC) 建模人类细分时钟和体生成.
  • 研究人类轴性骨发展的分子机制.
  • 探索基因在分段时钟功能和相关疾病中的特定作用.

主要方法:

  • 从人类iPSC中逐步在体外诱导甲状腺间皮.
  • 核心细分时钟基因振荡的分析 (例如,HES7,DKK1).
  • 在iPSC中进行CRISPR-Cas9基因组编辑以研究与疾病相关的基因 (HES7,LFNG,DLL3,MESP2).

主要成果:

  • 建立了一个大约五小时的人类分段时钟模型.
  • 在人体前皮层中观察到动态的,波形的基因表达模式.
  • 在人类和小鼠模型中确定了保存和特定物种的振荡基因.
  • 在患者衍生的iPSC中对振荡,同步和差异化表现出基因特异性影响.

结论:

  • 这项研究提供了人类细分时钟和体质生成的功能模型.
  • 这些发现阐明了涉及脊椎动物轴性骨模式的分子途径.
  • 这项研究提供了关于脊椎细分缺陷病变的见解,