P25 ELF5 regulation of normal skin development and homeostasis

Abstract Introduction and aims Skin development is regulated by complex programmes of gene activation and silencing of gene expression to maintain normal skin and hair development and homeostasis. E74-like factor (ELF)5 is a member of the E26 transformation-specific family of transcription factors and is expressed predominantly in epithelial cells and has been shown to regulate cellular processes such as proliferation, differentiation and maintenance of stem/progenitor cell populations in other epithelial cells/tissues. Our aim was to determine what role ELF5 had during skin development and homeostasis using both in vitro and ex vivo studies. Methods We observed that ELF5 is expressed predominantly in basal (stem/progenitor cells) and suprabasal (differentiated) layers of the epidermis. In hair follicles, ELF5 expression is found in bulge (stem/progenitor cells) and hair bulb regions (proliferative and differentiating keratinocytes). Using calcium-induced keratinocyte differentiation in primary human keratinocytes cells in vitro revealed that ELF5 can potentially regulate keratinocyte differentiation and proliferation processes. Results Our data provide a potentially important understanding of ELF5 as a crucial regulator and maintainer of stem/progenitor cell functions during normal human tissue homeostasis and regeneration. We performed RNA sequencing analysis of sorted GFP+ lentiviral in primary human keratinocytes (awaiting results) to investigate the impact of loss-or-gain of ELF5 expression in primary keratinocytes to determine the potential molecular targets of ELF5 in human keratinocytes. This will in turn help identify the potential regulatory mechanisms at play during proliferation, differentiation, apoptosis, migration, etc. in normal healthy human skin. Conclusions Our study provides an important foundation for further analyses of the role of ELF5 as a regulator of pathway activities in many areas of research, including regenerative medicine, and ageing.