Integrin-linked kinase regulates the niche of quiescent epidermal stem cells.
Integrin-linked kinase regulates the niche of quiescent epidermal stem cells.
复制标题
整联蛋白连接的激酶调节静态表皮干细胞的利基。
DOI：
10.1038/ncomms9198
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发表时间：
2015-09-08
影响因子：
16.6
通讯作者：
Wickström SA
中科院分区：
文献类型：
--
作者：
Morgner J;Ghatak S;Jakobi T;Dieterich C;Aumailley M;Wickström SA
干细胞存在于对其功能至关重要的专门小生境中。静止的毛囊干细胞（HFSC）被限制在隆突龛内，但龛的分子组成如何调节干细胞的行为知之甚少。在这里，我们表明，整合素连接激酶（ILK）是一个关键的调节凸起的细胞外基质微环境，从而管理激活和维持HFSCs。ILK介导在包裹毛囊的基底膜（BM）内的逆层粘连蛋白（LN）-332和LN-511梯度的沉积。精确的BM组成调节Wnt和转化生长因子-β途径的活性，并随后调节HFSC活化。值得注意的是，重建最佳LN微环境恢复了ILK缺陷细胞中改变的信号传导。在ILK缺陷的表皮中异常的干细胞活化导致增加的复制应激，使组织易于癌变。总体而言，我们的研究结果揭示了BM生态位在调节干细胞激活从而调节皮肤稳态方面的关键作用。 整合素连接激酶（ILK）已知调节细胞外基质和毛囊形态发生。Morgner等人发现，ILK的缺乏导致基底膜层粘连蛋白的比例异常，从而激活干细胞并使皮肤易发生癌变。
Stem cells reside in specialized niches that are critical for their function. Quiescent hair follicle stem cells (HFSCs) are confined within the bulge niche, but how the molecular composition of the niche regulates stem cell behaviour is poorly understood. Here we show that integrin-linked kinase (ILK) is a key regulator of the bulge extracellular matrix microenvironment, thereby governing the activation and maintenance of HFSCs. ILK mediates deposition of inverse laminin (LN)-332 and LN-511 gradients within the basement membrane (BM) wrapping the hair follicles. The precise BM composition tunes activities of Wnt and transforming growth factor-β pathways and subsequently regulates HFSC activation. Notably, reconstituting an optimal LN microenvironment restores the altered signalling in ILK-deficient cells. Aberrant stem cell activation in ILK-deficient epidermis leads to increased replicative stress, predisposing the tissue to carcinogenesis. Overall, our findings uncover a critical role for the BM niche in regulating stem cell activation and thereby skin homeostasis. Integrin-linked kinase (ILK) is known to modulate the extracellular matrix and hair follicle morphogenesis. Here, Morgner et al. show that lack of ILK causes an aberrant ratio of basement membrane laminins, activating stem cells and predisposing skin to carcinogenesis.