The Pattern of Cellular Organization of Human Epidermis

Mackenzie, Ian C.; Zimmerman, Karl; Peterson, Lawrence

doi:10.1111/1523-1747.ep12521107

Cited by 46 publications

(21 citation statements)

References 18 publications

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“…Various mammalian epidermis shows a regular interdigitation pattern in the SC (Christophers, 1972; Mackenzie et al, 1981), suggesting that the f-TKD cell turnover mechanism governs cell differentiation in mammals. Further investigation on whether this characteristic interdigitation pattern is observed in the SC of other vertebrates, such as amphibians, reptiles and birds, may reveal the general applicability of the f-TKD model to cornified stratified epithelia.…”

Section: Discussionmentioning

confidence: 99%

Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

Yokouchi

Atsugi

Logtestijn

et al. 2016

eLife

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In multicellular organisms, cells adopt various shapes, from flattened sheets of endothelium to dendritic neurons, that allow the cells to function effectively. Here, we elucidated the unique shape of cells in the cornified stratified epithelia of the mammalian epidermis that allows them to achieve homeostasis of the tight junction (TJ) barrier. Using intimate in vivo 3D imaging, we found that the basic shape of TJ-bearing cells is a flattened Kelvin's tetrakaidecahedron (f-TKD), an optimal shape for filling space. In vivo live imaging further elucidated the dynamic replacement of TJs on the edges of f-TKD cells that enables the TJ-bearing cells to translocate across the TJ barrier. We propose a spatiotemporal orchestration model of f-TKD cell turnover, where in the classic context of 'form follows function', cell shape provides a fundamental basis for the barrier homeostasis and physical strength of cornified stratified epithelia.DOI: http://dx.doi.org/10.7554/eLife.19593.001

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Section: Discussionmentioning

confidence: 99%

Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

Yokouchi

Atsugi

Logtestijn

et al. 2016

eLife

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“…The en-face view that the system used here generates appears to acquire rather homogeneous SC domains, based on the columnar stacking of corneocytes, where the vertical inter-corneocyte spaces are rather big. By comparison, the horizontal inter-corneocyte spaces are small, also compared to the corneocyte volume 5,22,21,42 ; the overall error through "mixing" of domains should therefore be small. Previously, we demonstrated that the Sodium-Hydrogen-Exchanger 1 (NHE1) plays a key role in establishing the critical acidic SC milieu 2 , and how generating this milieu is of key functional importance in the post-natal adaptation and maturation period of mammalian epidermis 1 .…”

Section: Discussionmentioning

confidence: 99%

Fluorescence lifetime to image epidermal ionic concentrations

Behne

Barry

Moll³

et al. 2004

SPIE Proceedings

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Measurements of ionic concentrations in skin have traditionally been performed with an array of methods which either did not reveal detailed localization information, or only provided qualitative, not quantitative information. FLIM combines a number of advantages into a method ideally suited to visualize concentrations of ions such as H + in intact, unperturbed epidermis and stratum corneum (SC). Fluorescence lifetime is dye concentration-independent, the method requires only low light intensities and is therefore not prone to photobleaching or phototoxic artifacts, and because multiphoton lasers of IR wavelength are used, light penetrates deep into intact tissue. The standard method to measure SC pH is the flat pH electrode, which provides reliable information only about surface pH changes, without further vertical or subcellular spatial resolution; i.e., specific microdomains such as the corneocyte interstices are not resolved, and the deeper SC is inaccessible without resorting to inherently disruptive stripping methods. Furthermore, the concept of a gradient of pH through the SC stems from such stripping experiments, but other confirmation for this concept is lacking. Our investigations into the SC pH distribution so far have revealed the crucial role of the Sodium/Hydrogen Antiporter NHE1 in generation of SC acidity, the colocalization of enzymatic lipid processing activity in the SC with acidic domains of the SC, and the timing and localization of emerging acidity in the SC of newborns. Together, these results have led to an improved understanding of the SC pH, its distribution, origin, and regulation. Future uses for this method include measurements of other ions important for epidermal processes, such as Ca 2+ , and a quantitative approach to topical drug penetration.

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“…Still, the physical dimensions of the two-photon focus, or the point-spread function of the microscopic system, limit the resolution and determination of intra-versus extracellular compartments within the SC. Nevertheless, the extracellular domains as present in the en-face view that this system generates should be rather homogeneous, based on the columnar stacking of corneocytes (45)(46)(47)(48), whereas the horizontal inter-corneocyte spaces are small compared with the corneocyte volume; the error based on the assignment of specific compartments should therefore be small.…”

Section: Nhe1 Regulates Epidermal Ph and Barrier Functionmentioning

confidence: 99%

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis

Behne

Meyer

Hanson

et al. 2002

Journal of Biological Chemistry

190

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The outermost epidermal layer, the stratum corneum (SC), exhibits an acidic surface pH, whereas the pH at its base approaches neutrality. NHE1 is the only Na ؉ /H ؉ antiporter isoform in keratinocytes and epidermis, and has been shown to regulate intracellular pH. We now demonstrate a novel function for NHE1, as we find that it also controls acidification of extracellular "microdomains" in the SC that are essential for activation of pH-sensitive enzymes and the formation of the epidermal permeability barrier. NHE1 expression in epidermis is most pronounced in granular cell layers, and although the surface pH of NHE1 knockout mice is only slightly more alkaline than normal using conventional pH measurements, a more sensitive method, fluorescence lifetime imaging, demonstrates that the acidic intercellular domains at the surface and of the lower SC disappear in NHE1 ؊/؊ animals. Fluorescence lifetime imaging studies also reveal that SC acidification does not occur through a uniform gradient, but through the progressive accumulation of acidic microdomains. These findings not only visualize the spatial distribution of the SC pH gradient, but also demonstrate a role for NHE1 in the generation of acidic extracellular domains of the lower SC, thus providing the acidification of deep SC interstices necessary for lipid processing and barrier homeostasis.

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The Pattern of Cellular Organization of Human Epidermis

Cited by 46 publications

References 18 publications

Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

Epidermal cell turnover across tight junctions based on Kelvin's tetrakaidecahedron cell shape

Fluorescence lifetime to image epidermal ionic concentrations

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis

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