维生素D受体与p63信号交叉交谈促进了表皮细胞命运
Yuko Oda1, Christian T Wong2, Dennis H Oh2
1Departments of Medicine and Endocrinology, United States.
概括
维生素D受体 (VDR) 对于表皮干细胞的命运至关重要,指导它们在受伤后再生毛囊间表皮. VDR与p63相互作用,通过超级增强剂影响基因调节,以进行适当的皮肤修复.
科学领域:
- 皮肤病学 皮肤病学
- 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:
- 维生素D受体 (VDR) 和它的配体1,25-二氧维生素D3 (1,25D3) 在表皮干细胞调节中发挥作用.
- 以前的研究表明,从角质细胞中去除VDR会延迟小鼠的皮肤伤口再上皮质化.
研究的目的:
- 研究VDR在Lrig1表达毛囊干细胞中在受伤后表皮再生中的作用.
- 阐明VDR在表皮干细胞命运决定中的功能背后的分子机制.
主要方法:
- 在小鼠Lrig1表达干细胞中Vdr的条件删除.
- 谱系追踪以追踪干细胞迁移和分化.
- 全基因组转录分析和发明之路分析 (IPA).
- 表观遗传学研究,包括VDR和p63同居化分析.
- 在没有p63的情况下,评估角质细胞对1,25(OH) 2D3的反应的功能测试.
主要成果:
- 毛囊干细胞中的VDR缺失阻止了它们的迁移和毛囊间表皮的再生,但不能阻止脂质腺的重新填充.
- 转录分析发现TP53家族,包括p63,是VDR的关键合作伙伴.
- 在表皮命运决定转录因子基因 (例如,Fos,Jun) 的超强增强器区域内同位于VDR和p63.
- 缺乏p63的角质细胞显示出表皮命运转录因子的减少表达,以应对1,25(OH) 2D3.
结论:
- VDR对于指导表皮干细胞命运向毛囊间表皮再生至关重要.
- VDR的功能涉及与主调节器 p63.63 的交叉通话.
- 这种相互作用是由影响关键表皮转录因子的超强增强器表观遗传动力学介导的.
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