Key Points
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The skin barrier is essential to protect animals from the external environment. The proper establishment of the skin barrier during embryogenesis and its maintenance during adult homeostasis is crucial for survival.
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Different modes of asymmetric stem cell (SC) division contribute to the development and the homeostasis of the skin barrier.
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Different populations of SCs reside in the skin epidermis and contribute to the homeostasis of the different epidermal compartments, such as the interfollicular epidermis, hair follicles and sebaceous glands.
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Slow-cycling hair follicle SCs form early during skin embryogenesis and are responsible for formation of the sebaceous glands, completion of hair follicle morphogenesis and efficient wound repair of epidermis.
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In the adult, hair follicle SCs are required for wound repair and for the normal cyclic bouts of hair growth that occur throughout life.
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The molecular mechanisms that govern embryonic development of the epidermis are reused during postnatal life to regulate harmoniously the balance between SC activation and differentiation, ensuring the homeostasis of the different compartments of the skin epidermis.
Abstract
The skin epidermis and its array of appendages undergo ongoing renewal by a process called homeostasis. Stem cells in the epidermis have a crucial role in maintaining tissue homeostasis by providing new cells to replace those that are constantly lost during tissue turnover or following injury. Different resident skin stem cell pools contribute to the maintenance and repair of the various epidermal tissues of the skin, including interfollicular epidermis, hair follicles and sebaceous glands. Interestingly, the basic mechanisms and signalling pathways that orchestrate epithelial morphogenesis in the skin are reused during adult life to regulate skin homeostasis.
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Acknowledgements
We thank our many colleagues in the field who contributed to our understanding of skin homeostasis. We apologize to those whose papers are not cited owing to space constraints. We thank W. Lowry, J. Nowak, Y. Hsu, P. Chi, M. Hack, G. Guasch, R. Yi, G. Lapouge and A. Vankeymeulen for their thoughtful comments and critical reading of the manuscript. C.B. is supported by the Human Frontiers in Science Program Organization (HFSPO), the Belgian Fund for Scientific Research (FRS/FNRS), Wallonia Region, the Schlumberger Foundation, and the European Research Council. E.F. is an investigator of the Howard Hughes Medical Institute and receives funding from the National Institutes of Health and the Starr Foundation.
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Glossary
- Hair follicle
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A skin appendage that produces a hair.
- Gastrulation
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A crucial stage during embryonic development that results in the formation of the three embryonic layers — ectoderm, endoderm and mesoderm — from which all tissues and organs arise.
- Dermis
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The mesenchymal part of the skin that is rich in collagen fibres and contains fibroblasts, blood vessels and immune cells.
- Intermediate filament
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(IF). A cytoskeletal filament that is 10 nm in diameter and exists in skin epithelium as a heteropolymer that is assembled from ∼10,000 individual keratin proteins of two distinct types. The IF network provides the epidermal cells with resistance against mechanical stress.
- Desmosome
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A robust cell–cell junction, which is composed of adhesive desmosomal transmembrane cadherins that associate intracellularly with two proteins — plakoglobin, which is a relative of β-catenin, and desmoplakin. These, in turn, link the structure to keratin intermediate filaments.
- Cornified
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The transformation of cells into a horny-like material, such as horn and nails.
- SC niche
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The specialized microenvironment that is necessary to support the maintenance and differentiation of stem cells (SCs).
- Mitotic spindle
-
The molecular apparatus that allows the segregation of chromosomes to daughter cells during cell division and is composed mainly of microtubules and proteins.
- Astral microtubule
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A microtubule that is nucleated at the spindle pole and grows outwards towards the cell cortex; it is involved in mitotic spindle positioning.
- Interfollicular epidermis
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The skin epidermis located between the emergence of the periodically spaced hair follicles.
- Sebaceous gland
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Attached to a hair follicle, this gland produces sebum, an oily substance that is made of lipids and cellular debris of sebaceous cells. The sebum helps to protect and waterproof the hair and the skin surface.
- Hair shaft
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The structure that is composed of terminally differentiated keratinocytes and emerges from the skin surface as a hair.
- Inner root sheath
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The inner channel of the hair shaft.
- Bulge
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A specialized portion of the hair follicle that contains multipotent stem cells that give rise to all hair follicle cell lineages as well as sebocytes and cells of the interfollicular epidermis during physio-pathological conditions.
- Hair germ
-
An outgrowth emanating from the bulge that forms during the early stage of hair follicle regeneration and corresponds to early committed progenies of bulge stem cells.
- Dermal papilla
-
The dermal part of the hair follicle, which consists of a small cluster of specialized fibroblast cells that have an instructive role to epithelial cells during hair follicle specification and regeneration.
- Outer root sheath
-
The external layer of the hair follicle that is contiguous with the basal layer of the interfollicular epidermis.
- Upper isthmus
-
The part of the hair follicle between the top of the bulge and the infundibulum, the uppermost part of the hair follicle that contacts the interfollicular epidermis.
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Blanpain, C., Fuchs, E. Epidermal homeostasis: a balancing act of stem cells in the skin. Nat Rev Mol Cell Biol 10, 207–217 (2009). https://doi.org/10.1038/nrm2636
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DOI: https://doi.org/10.1038/nrm2636
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