Organization of Stem Cells and Their Progeny in Human Epidermis

Abstract

Renewal of epidermis is achieved by an ordered replication of stem cells and transit amplifying cells followed by terminal differentiation. In mouse epidermis, renewal is organized around highly ordered structures termed epidermal proliferative units (EPU), each generated by a single stem cell. It has been difficult to apply these concepts to the human epidermis where the basal layer is undulating and the strata have variable thickness. For example, it is unclear whether stem cells in human epidermis are located at the base of rete ridges or overlying the tip of dermal papilla. Data are available to support both views. To gain a better understanding of EPU organization in human skin, we have genetically marked xenografts of human foreskin with a lentivirus encoding a fluorescent marker protein and have mapped labeled columns of cells over a 28-wk period. By following these columns to their origin in the epidermis we have been able to determine that stem cells are dispersed along the basal compartment. The widths of these columns do vary considerably, with the narrowest originating from cells located in the base of the rete ridge. These findings provide new insights into the dynamics of epidermal renewal in human glabrous skin.

A Stable Niche Supports Long-Term Maintenance of Human Epidermal Stem Cells in Organotypic Cultures

“…A dispersed distribution of stem cells would assist in this type of recovery. Our finding that LRCs are dispersed individually support the last possibility and agrees with several in vivo studies in which IFE healing was facilitated by dispersed epidermal stem cells [8,12,33].…”

“…Although expression patterns of ␤1 high MCSP high and ␣6 high CD71 low did not overlap, long-lived and highly clonogenic cells were present in both populations, suggesting that stem cells in the IFE may not be restricted to either of these two sites. Grafting LacZmarked human keratinocytes onto immune-deficient mice or infecting the keratinocytes directly on the backs of nude mice supported evidence that stem cells were intermittently distributed throughout the basal layer of human IFE [12,14,15].…”

Localization of bromodeoxyuridine-incorporating, p63- and p75NGFR- expressing cells in the human gingival epithelium

“…These sites in the basal layer probably contained stem cells, which play an essential role in the supply of gingival epithelial cells. Ghazizadeh et al (5) reported that stem cells were sparsely present along the basal compartment, and not in a certain limited area in the basal layer and each column generated by a single stem cell was called an "epidermal proliferative unit (EPU)". Furthermore, they observed that the widths of these columns vary considerably, with the narrowest one originating from the cells located at the base of the rete ridges.…”

“…For example, in the epidermis, there are stem cells that divide and generate themselves and transient amplifying cells, and then terminally differentiate after a discrete number of cell divisions (1)(2)(3). Such renewal has been shown to be concentrated around highly ordered structures termed epidermal proliferative units (EPU), each generated by a single stem cell (4,5). Similar to that in the epidermis, there might be proliferative units for renewal of the oral mucosal epithelium, however it is yet to be reported.…”

Attributes of adult stem cells

“…This notion was supported by the fact that integrin dull cells were more mobile on type IV collagen than integrin bri cells. However, following the fate of genetically marked cells in human epidermis has suggested instead that stem cells are scattered all along the basal layer, giving rise to cells that migrate solely upwards, forming columns of cells reminiscent of epidermal proliferative unit (EPU)-like structures [116].…”