Regenerative Medicine Program, Sprott Centre for Stem Cell Research at the Ottawa Hospital Research Institute, 501 Smyth Road-CCW5226, Ottawa, Ontario K1Y 8L6, Canada.
Stem Cell Rev Rep. 2011 Nov;7(4):927-34. doi: 10.1007/s12015-011-9243-9.
The intermediate filament keratin 15 (K15) is present in variable amounts in various stratified epithelia, but has also been reported to be a stem cell marker in the hair follicle. Using peptide specific antibodies, we evaluated the temporal and spatial distribution pattern of K15 expression/localization during normal epidermal development and initiation of hair follicle formation, and in the injured mature epidermis (e.g., during acute injury and repair and in tumorigenesis). During development, K15 expression is first localized to a subset of epidermal basal cells and the overlying periderm at E12.5, but its expression is seen throughout the basal layer by E15.5 and beyond. In hair follicle morphogenesis, initial peg formation occurs in a K15-null area at E14.5 and as peg elongation proceeds through to the mature hair follicle, K15 expression follows the leading edge with positive cells restricted to the outer root sheath. In an epidermal injury model, K15 is first up-regulated and associated with both the basal and suprabasal layers of the interfollicular epidermis then expression becomes sporadic and down-regulated before a basal layer-specific association is re-established in the repaired epidermis. During tumorigenesis, K15 is first mis-expressed, and is ultimately down-regulated. Our data suggest that K15 protein expression may reflect not only expression in a stem or progenitor cell subpopulation, but also reflects the activity and responsiveness of basal-like cells to loss of homeostasis of the epidermal differentiation program. Thus, the data suggest caution in using K15 alone to delineate epidermal stem cells, and underscore the need for further investigation of K15 and other markers in epidermal cell subpopulations.
中间丝角蛋白 15（K15）在各种分层上皮组织中以不同的量存在，但也被报道为毛囊中的干细胞标志物。使用肽特异性抗体，我们评估了 K15 表达/定位在正常表皮发育和毛囊形成起始、成熟表皮损伤（例如急性损伤和修复以及肿瘤发生期间）期间的时空分布模式。在发育过程中，K15 表达最初定位于 E12.5 时表皮基底层和上覆的周皮的一部分，但在 E15.5 及以后，其表达可见于整个基底层。在毛囊形态发生过程中，最初的钉状突起形成于 E14.5 时的 K15 缺失区域，随着钉状突起延伸至成熟的毛囊，K15 表达跟随前缘，阳性细胞仅限于外根鞘。在表皮损伤模型中，K15 首先上调并与毛囊间表皮的基底层和超基底层相关，然后表达变得零星并下调，然后在修复表皮中重新建立基底层特异性关联。在肿瘤发生过程中，K15 首先异常表达，最终下调。我们的数据表明，K15 蛋白表达不仅反映了干细胞或祖细胞亚群中的表达，还反映了基底样细胞对表皮分化程序失去平衡的活性和反应性。因此，数据表明在单独使用 K15 来描绘表皮干细胞时要谨慎，并强调需要进一步研究 K15 和表皮细胞亚群中的其他标志物。
