Distinct contribution of stem and progenitor cells to epidermal maintenance

Distinct contribution of stem and progenitor cells to epidermal maintenance
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DOI:
10.1038/nature11393
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发表时间:
2012-09-13
期刊:
影响因子:
64.8
通讯作者:
Blanpain, Cedric
Blanpain, Cedric
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mascre, Guilhem;Dekoninck, Sophie;Blanpain, Cedric

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毛囊间表皮(IFE)是抵御外界环境的第一道屏障,其维持对生存至关重要。为解释IFE内稳态,已经提出了两种看似相反的理论。一种理论认为,IFE由长寿的慢周期干细胞维持,这些干细胞产生短暂扩充细胞后代;而另一种理论则表明,内稳态是由单一的定向祖细胞群通过平衡随机命运来实现的。在此,我们利用两种不同的可诱导Cre重组酶 - 雌激素受体构建体(靶向小鼠的IFE祖细胞)来探究IFE内的细胞异质性。对克隆命运数据和增殖动力学的定量分析表明,存在两个不同的增殖细胞区室,它们按等级排列,涉及慢周期干细胞和定向祖细胞。受伤后,只有干细胞对组织的修复和长期再生有重要贡献,而定向祖细胞的贡献有限。
The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by long-lived slow-cycling stem cells that give rise to transit-amplifying cell progeny, whereas the other suggests that homeostasis is achieved by a single committed progenitor population that balances stochastic fate. Here we probe the cellular heterogeneity within the IFE using two different inducible Cre recombinase-oestrogen receptor constructs targeting IFE progenitors in mice. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments arranged in a hierarchy involving slow-cycling stem cells and committed progenitor cells. After wounding, only stem cells contribute substantially to the repair and long-term regeneration of the tissue, whereas committed progenitor cells make a limited contribution.