Abstract
The epidermis is a self-renewing tissue. The balance between proliferation and differentiation processes is tightly regulated to ensure the maintenance of the stem cell (SC) population in the epidermis during life. Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of SC self-renewal in several tissues and its deregulation may result in aging or tumor development. Keratinocytes are equipped with several epigenetic enzymes and transcription factors that shape the gene expression signatures of different epidermal layers and allow dynamic and coordinated expression changes to finely balance keratinocyte self-renewal and differentiation. These factors converge their activity in the basal layer to repress p16INK4a expression, protecting cells from senescence, and preserving epidermal homeostasis and regeneration. Several stress stimuli may activate p16INK4a expression that orchestrates cell cycle exit and senescence response. In the present review, we discuss the role of p16INK4a regulators in human epidermal SC self-renewal, aging and cancer.
Highlights
Aging and cancer may be considered related endpoints of accumulating damages within epidermal self-renewing compartment. p16INK4a is a potent inhibitor of the G1/S-phase transition of the cell cycle. p16INK4a governs the processes of stem cell (SC) self-renewal in several tissues and its deregulation may result in aging or tumor development
The epidermis is a self-renewing tissue characterized by several compartmentalized layers of keratinocytes in stages of progressive differentiation by virtue of a temporal and spatial gene regulation: Namely, the basal layer is composed by proliferating keratinocytes; the upper layers are composed by viable and differentiated cells; the horny layer is composed by terminally differentiated cells [1]
Epidermal homeostasis relies on keratinocyte stem cells (SCs) hosted in the basal layer; they provide new cells to replace those lost during tissue turnover or following injury
Summary
The epidermis is a self-renewing tissue characterized by several compartmentalized layers of keratinocytes in stages of progressive differentiation by virtue of a temporal and spatial gene regulation: Namely, the basal layer is composed by proliferating keratinocytes; the upper layers are composed by viable and differentiated cells; the horny layer is composed by terminally differentiated cells [1]. Epidermal homeostasis relies on keratinocyte stem cells (SCs) hosted in the basal layer; they provide new cells to replace those lost during tissue turnover or following injury. SC properties comprise both the long term self-renewal ability and the differentiation capability [1]
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