Microenvironmental regulation of the tissue regenerative capacity of keratinocyte stem cells and their progeny.

皮肤的保护性外层被称为表皮，属于身体中一组快速翻转的组织。大多数表皮细胞的寿命只有2-3周，并作为成熟细胞从皮肤表面脱落。这些细胞被依赖于生长因子和黏附分子(以及其他信号)的持续细胞再生所取代。最近发现，皮肤的结缔组织，即真皮，位于表皮细胞的正下方，在提供一些生长和成熟所需的这些因子方面起着关键作用。事实上，越来越清楚的是，表皮和真皮细胞相互合作，调节表皮的增殖和成熟。我们实验室最近的工作表明，这种合作可能会产生一种新识别的黏附蛋白Layinin-10，它可以刺激正常和肿瘤表皮细胞的生长。我们最近还发现了一个有趣的真皮细胞亚群，它可能在促进表皮细胞生长方面发挥作用。因此，建议的研究目的是研究层粘连蛋白-10和这一特定的真皮细胞亚群在表皮增殖和成熟中的作用。这些研究还可能提供对这些因素在皮肤癌中的作用的洞察。

The protective outer layers of the skin known as the epidermis belongs to a group of tissues in the body that are turning over at a rapid rate. The majority ofepidermal cells have a lifespan of just 2-3 weeks, and are shed as mature cells from the skin's surface. These cells are replaced by continuous cell regeneration which is dependent on growth factors and adhesive molecules (and other signals). It has recently come to light that the connective tissue of the skin i.e. the dermis, which lies directly below the epidermal cells has a critical role in providing some of these factors required for their growth and maturation. Indeed, it is becoming increasingly clear that the epidermal and dermal cells co-operate to regulate epidermal proliferation and maturation. Recent work from our laboratory has shown that a newly recognised adhesive protein laminin-10 may be produced as the result of such co-operation and that it stimulates the growth of both normal and tumour epidermal cells. We have also recently identified an interesting subset of dermal cells that may have a role in promoting the growth of the epidermal cells. Thus, the aims of the proposed stuides are to investigate the role of laminin-10 and this specific dermal cell subset in epidermal proliferation and maturation. These studies may also provide an insight into the role of these factors in skin cancers.