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  • Stem cell–A progenitor cells that can both self-renew and give rise to differentiated progeny for an extended period of time.

  • Niche–The tissue microenvironment in which a stem cell resides that provides chemical and mechanical cues for the maintenance and regulation of the stem cell.

  • Transit amplifying cell–Quickly dividing cells that give rise to differentiated progeny. They are usually not long-lived.

  • Basal cells–The proliferative cells of the epidermis that form the innermost layer that attaches to the basement membrane.

  • Spinous cells–The first differentiated layers of the epidermis. They are post-mitotic and enriched in desmosomes.

  • Granular cell–Differentiated cells of the epidermis that contain keratohyalin granules that contain precursors for the cornified envelope. These cells form tight junctions that provide some of the barrier activity of the epidermis.

  • Stratum corneum–The terminally differentiated layers of the superficial epidermis. It is composed of cornified envelopes, highly crosslinked meshworks of protein cemented together by specialized lipids that provides a barrier to the external environment.

  • Epigenetics–Control of gene expression by modifications in chromatin, including post-translational modifications of DNA or histones, or chromatin remodeling.



  • Epidermal homeostasis and wound healing are driven by proliferation of stem/progenitor cells in the basal layer.

  • Epidermal differentiation is a tightly regulated process that is controlled by the interplay between transcription factors, chromatin modifiers, and posttranscriptional regulators.

  • Terminal differentiation results in 2 barriers, tight junctions and the cornified envelopes, which protect us from the external environment.


The epidermis must maintain a largely impenetrable barrier to the outside world over the course of a lifetime. Simultaneously, it rapidly turns over, replacing itself every 2 weeks, and retains the ability to heal wounds. To accomplish these divergent roles, the epidermis has a highly regulated proliferation/differentiation program. Progenitor cells within the basal layer of the epidermis have a very high capacity for proliferation and self-renewal, whereas the major role for differentiated cells is generation of a barrier. In this chapter, we will discuss the current understanding of the roles of stem cells in interfollicular epidermis, how proliferation is controlled in basal cells, and how multiple pathways and structures collaborate to generate an epidermal barrier. Of note, some of these findings are drawn from studies in mouse skin, which is architecturally distinct from human epidermis. However, in many cases, there are studies of cultured human cells or human disease correlates that substantiate some of the findings in mice.



Stem cells are progenitor cells that can both renew themselves and give rise to differentiated progeny over an extended time period. The ability of the epidermis to continually regenerate itself and to heal wounds indicates that it must contain stem cells. Further, the pioneering work of Howard Green and colleagues allowed for the growth of these epidermal stem cells in culture, which was a ...

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