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

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.

Keywords: 5-hydroxymethylcytosine (5-hmC); bulge activation; cytokeratin 15 (CK15); epigenetics.

MeSH terms

  • 5-Methylcytosine / analogs & derivatives*
  • 5-Methylcytosine / metabolism
  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation*
  • Cell Proliferation*
  • Epigenesis, Genetic / physiology*
  • Hair Follicle / cytology
  • Hair Follicle / metabolism*
  • Humans
  • Keratin-15 / metabolism
  • Mice
  • Stem Cells / cytology
  • Stem Cells / metabolism*

Substances

  • Biomarkers
  • Keratin-15
  • 5-hydroxymethylcytosine
  • 5-Methylcytosine