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用于体内定量监测经典 Wnt 信号的转基因闪光小鼠,以跟踪毛囊周期动态。

Transgenic flash mice for in vivo quantitative monitoring of canonical Wnt signaling to track hair follicle cycle dynamics.

机构信息

Experimental Dermatology Group, UQ Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.

Department of Physics and Mathematics, The University of Queensland, Brisbane, Queensland, Australia.

出版信息

J Invest Dermatol. 2014 Jun;134(6):1519-1526. doi: 10.1038/jid.2014.92. Epub 2014 Feb 14.

DOI:10.1038/jid.2014.92
PMID:24531689
Abstract

Hair follicles (HFs) upon development enter a lifelong cycle of growth, regression, and resting. These phases have been extensively studied at the cellular and molecular levels for individual HFs. However, HFs group into domains with coordinated cycling strongly influenced by their environment. These macroscopic hair domains have been difficult to study and can be influenced by physiological or pathological conditions, such as pregnancy or skin wounds. To robustly address this issue, we generated a mouse model for quantitative monitoring of β-catenin activity reflecting HF cycle dynamics macroscopically by using live bioluminescence imaging. These mice allowed live tracking of HF cycles and development, and highlighted hair regenerative patterns known to occur through macro-environmental cues, including initiation events, propagating anagen and border stability, and allowed refinement of a mechanistic mathematical model that integrates epidermal cell population dynamics into an excitable reaction-diffusion model. HF cycling could be studied in situations of pregnancy, wound healing, hair plucking, as well as in response to cyclosporine or Wnt3a stimulation. In conclusion, we developed a model for analysis of HF cycling at the macroscopic level that will allow refined analysis of hair cycle kinetics as well as its propagation dynamics.

摘要

毛囊(HFs)在发育过程中进入生长、退化和静止的终身循环。这些阶段在单个 HFs 的细胞和分子水平上已经得到了广泛的研究。然而,HFs 成群结队地进入周期性循环,这些循环受到其环境的强烈影响。这些宏观的头发区域很难研究,并且可能受到生理或病理条件的影响,例如怀孕或皮肤伤口。为了有效地解决这个问题,我们通过使用活体生物发光成像生成了一种用于定量监测β-连环蛋白活性的小鼠模型,该模型反映了宏观上 HF 周期动力学。这些老鼠允许对 HF 周期和发育进行活体追踪,并突出了已知通过宏观环境线索发生的毛发再生模式,包括启动事件、推进生长期和边界稳定性,并允许对将表皮细胞群体动力学整合到兴奋反应扩散模型中的机制数学模型进行细化。HF 循环可以在怀孕、伤口愈合、拔毛以及对环孢素或 Wnt3a 刺激的情况下进行研究。总之,我们开发了一种用于分析宏观水平 HF 循环的模型,该模型将允许对毛发周期动力学及其传播动力学进行更精细的分析。

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Temporal Regulation of Natural Killer T Cell Interferon Gamma Responses by β-Catenin-Dependent and -Independent Wnt Signaling.β-连环蛋白依赖性和非依赖性 Wnt 信号对自然杀伤 T 细胞干扰素 γ 反应的时间调节。
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