The epidermis comprises autonomous compartments maintained by distinct stem cell populations.

The epidermis comprises autonomous compartments maintained by distinct stem cell populations.
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表皮包括由不同的干细胞种群维持的自主室。

DOI:
10.1016/j.stem.2013.07.010
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发表时间:
2013-10-03
期刊:
影响因子:
23.9
通讯作者:
Jensen, Kim B.
Jensen, Kim B.
中科院分区:
医学1区
文献类型:
--
作者:
Page, Mahalia E.;Lombard, Patrick;Ng, Felicia;Goettgens, Berthold;Jensen, Kim B.

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表皮复杂的解剖结构包含多种成体干细胞群,但在稳态、伤口愈合和肿瘤发生过程中它们在功能上重叠的程度仍不明确。在此,我们证明Lrig1阳性细胞是高度增殖的表皮干细胞。长期克隆分析显示,Lrig1阳性细胞维持毛囊皮脂腺上部单位,将漏斗部和皮脂腺作为独立的部分,但对毛囊和毛囊间表皮均无贡献,毛囊和毛囊间表皮由不同的干细胞群维持。相反,在受伤时,来自多个部分的干细胞后代获得谱系可塑性,并对再生组织有永久性贡献。我们进一步表明,Lrig1阳性细胞中的癌基因激活会导致增生,但肿瘤形成需要辅助刺激。总之,我们的数据表明表皮干细胞在稳态时受谱系限制,并提示分区化可能是上皮组织维持的一种保守机制。 Lrig1标记表皮中具有独特谱系潜能的干细胞 表皮由多个干细胞群在不同的部分进行维持 分区化而非层级结构是组织复杂性维持的基础 受伤会改变干细胞命运并增强致癌反应 表皮被划分为由不同干细胞群维持的自主部分,Lrig1阳性干细胞是漏斗部和皮脂腺补充的来源
The complex anatomy of the epidermis contains multiple adult stem cell populations, but the extent to which they functionally overlap during homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we demonstrate that Lrig1+ve cells are highly proliferative epidermal stem cells. Long-term clonal analysis reveals that Lrig1+ve cells maintain the upper pilosebaceous unit, containing the infundibulum and sebaceous gland as independent compartments, but contribute to neither the hair follicle nor the interfollicular epidermis, which are maintained by distinct stem cell populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1+ve cells drives hyperplasia but requires auxiliary stimuli for tumor formation. In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance. Lrig1 marks stem cells in the epidermis with a unique lineage potential Epidermis is maintained in discrete compartments by multiple stem cell populations Compartmentalization, not hierarchy, underlies maintenance of tissue complexity Wounding alters stem cell fate and potentiates the oncogenic response The epidermis is divided into autonomous compartments maintained by distinct stem cell populations, and Lrig1+ stem cells are the source of infundibulum and sebaceous gland replenishment.
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