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表观遗传标记5-羟甲基胞嘧啶的差异分布在毛囊凸起激活过程中出现在毛囊干细胞中。

Differential distribution of the epigenetic marker 5-hydroxymethylcytosine occurs in hair follicle stem cells during bulge activation.

作者信息

Leavitt Danielle, Wells Michael, Abarzua Phammela, Murphy George F, Lian Christine G

机构信息

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.

出版信息

J Cutan Pathol. 2019 May;46(5):327-334. doi: 10.1111/cup.13434. Epub 2019 Apr 1.

Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

摘要

背景

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。

方法

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。

结果

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。

结论

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。

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