Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Physics, Graduate School of Science, Chiba University, Chiba, Japan.
Lab Invest. 2022 Jun;102(6):581-588. doi: 10.1038/s41374-022-00738-2. Epub 2022 Feb 10.
Vertebrates exhibit patterned epidermis, exemplified by scales/interscales in mice tails and grooves/ridges on the human skin surface (microtopography). Although the role of spatiotemporal regulation of stem cells (SCs) has been implicated in this process, the mechanism underlying the development of such epidermal patterns is poorly understood. Here, we show that collagen XVII (COL17), a niche for epidermal SCs, helps stabilize epidermal patterns. Gene knockout and rescue experiments revealed that COL17 maintains the width of the murine tail scale epidermis independently of epidermal cell polarity. Skin regeneration after wounding was associated with slender scale epidermis, which was alleviated by overexpression of human COL17. COL17-negative skin in human junctional epidermolysis bullosa showed a distinct epidermal pattern from COL17-positive skin that resulted from revertant mosaicism. These results demonstrate that COL17 contributes to defining mouse tail scale shapes and human skin microtopography. Our study sheds light on the role of the SC niche in tissue pattern formation.
脊椎动物表现出有图案的表皮，以小鼠尾巴上的鳞片/鳞片之间和人类皮肤表面的凹槽/脊（微观形貌）为例。尽管时空调节干细胞（SCs）的作用已被牵涉到这个过程中，但这种表皮模式发育的机制还知之甚少。在这里，我们表明，表皮干细胞的龛位胶原 XVII（COL17）有助于稳定表皮模式。基因敲除和挽救实验表明，COL17 独立于表皮细胞极性维持小鼠尾巴鳞片表皮的宽度。创伤后皮肤再生与细长的鳞片表皮有关，而过表达人 COL17 可减轻这种情况。人交界性大疱性表皮松解症中缺乏 COL17 的皮肤与 COL17 阳性皮肤表现出不同的表皮模式，这是由于回复嵌合体造成的。这些结果表明 COL17 有助于确定小鼠尾巴鳞片的形状和人类皮肤的微观形貌。我们的研究揭示了 SC 龛在组织模式形成中的作用。
