Abstract

Stem cell markers of interfollicular epidermis (IEF) have not been established thus far. The aim of this study is to suggest a new way to disclose IFE-stem cells by combining the expression of histone deacetylases (HDAC) 1 and p63. Immunohistochemical staining of HDAC1 and p63 was performed in six normal human samples. Moreover, a skin equivalent (SE) model was treated with suberoylanilohydroxamic acid (SAHA, an HDAC inhibitor) to elucidate the role of HDAC1. Finally, rapidly adhering (RA) keratinocytes to a type IV collagen, which have been identified to represent epidermal stem cells, were subjected to Western blot analysis with antibodies against HDAC1. In normal samples, there was a minor subpopulation comprised of p63-positive and HDAC1-negative cells in the basal layers. The proportion of this subpopulation was decreased with age. In the SE model, SAHA treatment increased the epidermal thickness and number of p63-positive cells in a dose dependent manner. After SAHA treatment, the expression of differentiation markers was decreased, while that of basement membrane markers was increased. In a Western blot analysis, HDAC1 was not expressed in RA cells. In conclusion, the combination of p63-positive and HDAC1-negative expressions can be a potential new way for distinguishing epidermal stem cells.

Highlights

  • The epidermal stem cells (ESC) play a critical role in the maintenance and regeneration of cutaneous epithelial tissues

  • P63 was most strongly expressed in the basal layer, with moderate expression in the upper layer; the staining intensity decreased as the layer increased, and the cells in the granular layer were rarely stained

  • There was a subpopulation showing a p63-positive/HDAC1-negative staining pattern in the basal layer, and the number of these cells decreased gradually with age

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Summary

Introduction

The epidermal stem cells (ESC) play a critical role in the maintenance and regeneration of cutaneous epithelial tissues. Stem cells in the IFE are expected to play a more important role in skin tissue homeostasis. These cells are thought to be dispersed along the basement membrane, which is a complex network of extracellular matrix (ECM) molecules interacting through integrins. This interaction between integrins and ECM may be important in shaping the epidermal stem cell niche [8]

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