Building and Maintaining the Skin

Hsu, Ya‐Chieh; Fuchs, Elaine

doi:10.1101/cshperspect.a040840

Cited by 56 publications

(40 citation statements)

References 137 publications

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“…Our finding that SEDC genes of caecilians are expressed in the skin but not, or only at low levels, in other organs, indicates that these EDC genes, like their counterparts in amniotes, are specifically important for the body’s barrier against the environment, i.e. the primordial function of the skin 3 , 34 . Each species of caecilians investigated has at least two SEDC genes with distinct amino acid sequences (Fig.…”

Section: Discussionmentioning

confidence: 88%

Evolutionary diversification of epidermal barrier genes in amphibians

Sachslehner

Eckhart

2022

Sci Rep

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The epidermal differentiation complex (EDC) is a cluster of genes encoding components of the skin barrier in terrestrial vertebrates. EDC genes can be categorized as S100 fused-type protein (SFTP) genes such as filaggrin, which contain two coding exons, and single-coding-exon EDC (SEDC) genes such as loricrin. SFTPs are known to be present in amniotes (mammals, reptiles and birds) and amphibians, whereas SEDCs have not yet been reported in amphibians. Here, we show that caecilians (Amphibia: Gymnophiona) have both SFTP and SEDC genes. Two to four SEDC genes were identified in the genomes of Rhinatrema bivittatum, Microcaecilia unicolor and Geotrypetes seraphini. Comparative analysis of tissue transcriptomes indicated predominant expression of SEDC genes in the skin of caecilians. The proteins encoded by caecilian SEDC genes resemble human SEDC proteins, such as involucrin and small proline-rich proteins, with regard to low sequence complexity and high contents of proline, glutamine and lysine. Our data reveal diversification of EDC genes in amphibians and suggest that SEDC-type skin barrier genes have originated either in a common ancestor of tetrapods followed by loss in Batrachia (frogs and salamanders) or, by convergent evolution, in caecilians and amniotes.

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Section: Discussionmentioning

confidence: 88%

Evolutionary diversification of epidermal barrier genes in amphibians

Sachslehner

Eckhart

2022

Sci Rep

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“… 7 Skin contains a number of different types of stem cells. 8 These include quiescent hair follicle bulge stem cells, which are intermittently activated to supply cells for the growing hair follicles, as well as actively proliferating Lgr5-positive stem- and progenitor cells of the secondary hair germ ( Fig. 1A ).…”

Section: Adult Epithelial Stem Cellsmentioning

confidence: 99%

How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells

2023

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First described in the early 20 th century, diurnal oscillations in stem cell proliferation exist in multiple internal epithelia, including in the gastrointestinal track, and in the epidermis. In the mouse epidermis, 3- to 4-fold more stem cells are in S-phase during the night than during the day. Work that is more recent showed that an intact circadian clock intrinsic to keratinocytes is required for these oscillations in epidermal stem cell proliferation. The circadian clock also regulates DNA excision repair and DNA-damage in epidermal stem cells in response to ultraviolet B radiation. During skin inflammation, epidermal stem cell proliferation is increased and diurnal oscillations are suspended. Here we discuss possible reasons for the evolution of this stem cell phenomenon. We argue that the circadian clock coordinates intermediary metabolism and the cell cycle in epidermal stem cells to minimize accumulation of DNA damage from metabolism-generated reactive oxygen species. Circadian disruption, common in modern society, leads to asynchrony between metabolism and the cell cycle, and we speculate this will lead to oxidative DNA damage, dysfunction of epidermal stem cells, and skin aging.

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“…For example, fibroblast proliferation is required for ECM remodeling ( Plikus et al, 2021 ); endothelial cell proliferation is required to revascularize regenerating tissue ( Pecoraro et al, 2021 ); hepatocytes proliferate to rebuild liver mass ( Chen et al, 2020 ); and multiple cell types proliferate after acute and chronic lung injury ( Kotton and Morrisey, 2014 ). In mammals, injury increases proliferation through a variety of mechanisms, including by stimulating division of tissue-resident stem cell populations ( Hsu and Fuchs, 2021 ); promoting cell cycle re-entry of quiescent stem cells ( Fu et al, 2015 ); activating facultative stem cells that normally exist in a fully differentiated state ( Leach and Morrisey, 2018 ); and expanding rare injury-responsive subpopulations ( Wilson et al, 2008 ; Ayyaz et al, 2019 ). Because depletion of stem and progenitor cells would compromise regeneration, proliferation must also balance renewal of the pool of cycling cells and maintenance of their pluripotency with production of post-mitotic progeny (discussed in Section 4.6 ) ( Feige et al, 2018 ; Gehart and Clevers, 2019 ).…”

Section: Extracellular Vesicles Promote Cellular Behaviors Required F...mentioning

confidence: 99%

An Emerging Frontier in Intercellular Communication: Extracellular Vesicles in Regeneration

Avalos

Forsthoefel

2022

Front. Cell Dev. Biol.

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Regeneration requires cellular proliferation, differentiation, and other processes that are regulated by secreted cues originating from cells in the local environment. Recent studies suggest that signaling by extracellular vesicles (EVs), another mode of paracrine communication, may also play a significant role in coordinating cellular behaviors during regeneration. EVs are nanoparticles composed of a lipid bilayer enclosing proteins, nucleic acids, lipids, and other metabolites, and are secreted by most cell types. Upon EV uptake by target cells, EV cargo can influence diverse cellular behaviors during regeneration, including cell survival, immune responses, extracellular matrix remodeling, proliferation, migration, and differentiation. In this review, we briefly introduce the history of EV research and EV biogenesis. Then, we review current understanding of how EVs regulate cellular behaviors during regeneration derived from numerous studies of stem cell-derived EVs in mammalian injury models. Finally, we discuss the potential of other established and emerging research organisms to expand our mechanistic knowledge of basic EV biology, how injury modulates EV biogenesis, cellular sources of EVs in vivo, and the roles of EVs in organisms with greater regenerative capacity.

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Building and Maintaining the Skin

Cited by 56 publications

References 137 publications

Evolutionary diversification of epidermal barrier genes in amphibians

Evolutionary diversification of epidermal barrier genes in amphibians

How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells

An Emerging Frontier in Intercellular Communication: Extracellular Vesicles in Regeneration

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