Leavitt Danielle, Wells Michael, Abarzua Phammela, Murphy George F, Lian Christine G
Department of Life Sciences, Program in Human Developmental and Regenerative Biology, Harvard College, Cambridge, Massachusetts.
Department of Pathology, Program in Dermatopathology, Brigham and Women's Hospital, Boston, Massachusetts.
J Cutan Pathol. 2019 May;46(5):327-334. doi: 10.1111/cup.13434. Epub 2019 Apr 1.
Hair follicle (HF) cycling is dependent upon activation and differentiation of an epithelial subpopulation of cells with stem-like characteristics. These cells express cytokeratin 15 (CK15) and are sequestered within a specialized niche termed the follicular bulge. The pathways that mediate bulge activation are poorly understood, although growing evidence suggests a role for epigenetic events.
Here we investigated murine and human HFs to determine whether a recently described epigenetic hydroxymethylation marker, 5-hmC, known to mediate cell growth and differentiation, may play a role in bulge activation.
We found the bulge region of murine HFs to show variable 5-hmC distribution within the nuclei of CK15-positive stem cells during early anagen, a pattern that was not associated with resting stem cells of telogen follicles, which did not express 5-hmC. Moreover, during phases of early anagen that were induced in an organ culture model, spatial alterations in bulge stem cell 5-hmC reactivity, as assessed by dual labeling, were noted.
These preliminary findings suggest that 5-hmC may play a dynamic role in bulge activation during anagen growth, and provide a foundation for further experimental inquiry into epigenomic regulation of HF stem cells.
毛囊(HF)循环依赖于具有干细胞样特征的上皮细胞亚群的激活和分化。这些细胞表达细胞角蛋白15(CK15),并被隔离在一个称为毛囊隆突的特殊微环境中。尽管越来越多的证据表明表观遗传事件发挥作用,但介导隆突激活的途径仍知之甚少。
在此,我们研究了小鼠和人类毛囊,以确定一种最近描述的表观遗传羟甲基化标记物5-羟甲基胞嘧啶(5-hmC)是否可能在隆突激活中发挥作用,已知该标记物可介导细胞生长和分化。
我们发现,在生长期早期,小鼠毛囊的隆突区域在CK15阳性干细胞的细胞核内显示出可变的5-hmC分布模式,而这种模式与休止期毛囊中不表达5-hmC的静止干细胞无关。此外,在器官培养模型诱导的生长期早期阶段,通过双重标记评估发现,隆突干细胞5-hmC反应性存在空间变化。
这些初步发现表明,5-hmC可能在生长期毛囊生长过程中的隆突激活中发挥动态作用,并为进一步研究毛囊干细胞的表观基因组调控提供了实验基础。