在一个共享的利基中,NFIB是表皮质-黑色素细胞干细胞行为的一个统治者
Chiung-Ying Chang1, H Amalia Pasolli, Eugenia G Giannopoulou
1Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, New York 10065, USA.
Nature
|February 8, 2013
概括
转录因子NFIB协调毛囊干细胞的同步. 在小鼠中的Nfib缺乏破坏了这一点,促进了黑色素细胞干细胞分化而不影响头发循环,揭示了关键的利基交叉机制.
科学领域:
- 干细胞生物学 干细胞生物学
- 皮肤病学 皮肤病学
- 分子遗传学 分子遗传学
背景情况:
- 哺乳动物毛囊中的成年干细胞通过利基线索维持组织平衡.
- 毛囊干细胞和黑色素细胞干细胞协调进行头发再生和染色.
- 剖析干细胞交叉交叉是具有挑战性的,因为血统特异性突变.
研究的目的:
- 确定毛囊干细胞同步的新型调节者.
- 研究转录因子NFIB在协调干细胞行为的作用.
- 阐明毛囊的干细胞间沟通的机制.
主要方法:
- 在小鼠毛囊干细胞中对Nfib的条件遗传向.
- 分析头发周期,毛囊结构和黑色素细胞干细胞行为.
- 染色体免疫沉与高通量测序 (ChIP-seq) 和转录分析.
- 药理上抑制内甲蛋白和KIT信号通路.
主要成果:
- 毛囊干细胞中的Nfib缺乏将干细胞同步脱离,而不会改变头发的循环.
- 缺乏Nfib的小鼠表现出增强的黑色素细胞干细胞增殖和分化,早期产生黑色素.
- 鉴定出KIT-连接体作为皮肤乳头信号,促进黑色素细胞干细胞分化.
- 确定为NFIB目标基因的内末林2 (Edn2),在NFIB缺乏干细胞中异常激活.
- 异位Edn2诱导NFIB缺陷的表型;内啡林/KIT抑制拯救了这些表型.
结论:
- NFIB是毛囊和黑色素细胞干细胞行为的关键协调者.
- 在NFIB缺少干细胞中异常的Edn2表达驱动着早期的黑色素细胞分化.
- 干细胞间的交叉通讯,通过诸如KIT连接体和内甲蛋白信号传递等因素调解,对于利基功能至关重要.
- 了解这些机制,可以了解头发变白,压力和与疾病相关的毛囊功能障碍.
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