Revisiting the significance of keratin expression in complex epithelia

Cohen, Erez; Johnson, Craig; Redmond, Catherine J.; Nair, Raji R.

doi:10.1101/2022.07.27.501769

Cited by 3 publications

(5 citation statements)

References 74 publications

(118 reference statements)

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“…The proliferating/mitotic KC cluster was defined by elevated expression of cell cycle regulator genes, such as RRM2, PTTG1, CDC20, TYMS, and HIST1H4C . KRT1 gene expression was already detectable in mitotic KCs and was most abundant in granular KCs (clusters granular 1 and 2), as described previously (Cohen et al, 2022). The granular KC clusters granular 1 and granular 2 and spinous KC specifically expressed KRT10, CDH1, EPHA2, and the desmosome-specific genes desmoglein (DSG1) and desmocollin (DSC1) at various levels (Figure 1D) .…”

Section: Kc Subsets In the Human Skinsupporting

confidence: 80%

“…KRT6 and KRT16 are involved in danger sensing via DAMPs and their expression levels have been shown to be elevated in stressed KC during wound healing and chronic skin inflammation (DePianto and Coulombe, 2004;Hobbs et al, 2012;Rotty and Coulombe, 2012;Lessard et al, 2013). KRT15, in contrast, is expressed in the hair bulge and in undifferentiated KCs of the basal layer Cohen et al, 2022). Hence, our data suggest that Der p 2 peptides induce perturbations in KC differentiation and keratinization in basal, suprabasal, and hair follicle KCs.…”

Section: Der P 2-derived Peptides Upregulate Il18 and Downregulate Kr...mentioning

confidence: 65%

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Epithelial Barrier Dysfunction in Disease

Pardo-Pastor,

López Posadas,

Ortiz Zapater

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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Section: Kc Subsets In the Human Skinsupporting

confidence: 80%

Section: Der P 2-derived Peptides Upregulate Il18 and Downregulate Kr...mentioning

confidence: 65%

Epithelial Barrier Dysfunction in Disease

Pardo-Pastor,

López Posadas,

Ortiz Zapater

2024

Frontiers Research Topics

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show abstract

“…KRT6 and KRT16 are involved in danger sensing via DAMPs and their expression levels have been shown to be elevated in stressed KC during wound healing and chronic skin inflammation (DePianto and Coulombe, 2004;Hobbs et al, 2012;Rotty and Coulombe, 2012;Lessard et al, 2013). KRT15, in contrast, is expressed in the hair bulge and in undifferentiated KCs of the basal layer (Cheng et al, 2018;Cohen et al, 2022). Hence, our data suggest that Der p 2 peptides induce perturbations in KC differentiation and keratinization in basal, suprabasal, and hair follicle KCs.…”

Section: Der P 2-derived Peptides Upregulate Il18 and Downregulate Kr...mentioning

confidence: 68%

“…The proliferating/mitotic KC cluster was defined by elevated expression of cell cycle regulator genes, such as RRM2, PTTG1, CDC20, TYMS, and HIST1H4C (Wang et al, 2020). KRT1 gene expression was already detectable in mitotic KCs and was most abundant in granular KCs (clusters granular 1 and 2), as described previously (Cohen et al, 2022). The granular KC clusters granular 1 and granular 2 and spinous KC specifically expressed KRT10, CDH1, EPHA2, and the desmosome-specific genes desmoglein (DSG1) and desmocollin (DSC1) at various levels (Figure 1D) (Wang et al, 2020).…”

Section: Kc Subsets In the Human Skinmentioning

confidence: 84%

Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients

Pfisterer,

Wielscher,

Samardzic

et al. 2023

Front. Cell Dev. Biol.

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Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 cytokine-driven skin inflammation and epithelial barrier dysfunction. The latter is believed to allow the increased penetration of chemicals, toxins, and allergens into the skin. House dust mite allergens, particularly Der p 2, are important triggers in sensitized individuals with AD; the precise actions of these allergens in epithelial biology remain, however, incompletely understood. In this study, we compared the effects of the protein allergen Der p 2 and a mix of non-IgE-reactive Der p 2 peptides on skin cells using patch tests in AD patients and healthy participants. We then analyzed mRNA expression profiles of keratinocytes by single-cell RNA-sequencing. We report that existing barrier deficiencies in the non-lesional skin of AD patients allow deep penetration of Der p 2 and its peptides, leading to local microinflammation. Der p 2 protein specifically upregulated genes involved in the innate immune system, stress, and danger signals in suprabasal KC. Der p 2 peptides further downregulated skin barrier genes, in particular the expression of genes involved in cell–matrix and cell–cell adhesion. Peptides also induced genes involved in hyperproliferation and caused disturbances in keratinocyte differentiation. Furthermore, inflammasome-relevant genes and IL18 were overexpressed, while KRT1 was downregulated. Our data suggest that Der p 2 peptides contribute to AD initiation and exacerbation by augmenting hallmark features of AD, such as skin inflammation, barrier disruption, and hyperplasia of keratinocytes.

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“…3e-i). Regardless, this newly discovered hybrid population represents proliferating cells committed to differentiation 58–60 .…”

Section: Resultsmentioning

confidence: 99%

An interactive cellular ecosystem blocks epithelial transformation in naked mole-rat

Behm,

Baeza Centurión,

Penso-Dolfin

et al. 2023

Preprint

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The mechanisms underlying cancer resistance in long-lived organisms are largely unexplored. Here, we report how naked mole-rats (Heterocephalus glaber) resist tumorigenesis when exposed to potent skin carcinogens. Single-cell transcriptional analysis of homeostatic full-thickness naked mole-rat skin revealed higher epidermal turn-over, a distinct composition of dermal extracellular matrix (ECM) and fewer resident T-cells, when compared to mouse and human. Carcinogenic treatment of skin generated the expected mutational landscape, but unlike in the mouse, failed to stimulate T-cells or generate tumours. Instead, naked mole-rat accelerated epidermal turnover to shed mutant cells. At the same time, the ECM was extensively remodelled via enhanced anti-inflammatory communication among fibroblasts and between fibroblasts and epidermal cells, creating a tumour-suppressive microenvironment. We demonstrate that, in contrast to mouse, naked mole-rat dermal fibroblasts lack intrinsic tumour promoting capabilities in vitro and in vivo. Our results demonstrate that the cellular ecosystem of naked mole-rat skin actively suppresses epithelial transformation.

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Revisiting the significance of keratin expression in complex epithelia

Cited by 3 publications

References 74 publications

Epithelial Barrier Dysfunction in Disease

Epithelial Barrier Dysfunction in Disease

Non-IgE-reactive allergen peptides deteriorate the skin barrier in house dust mite-sensitized atopic dermatitis patients

An interactive cellular ecosystem blocks epithelial transformation in naked mole-rat

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