Assessment of Spatial and Temporal Variation in the Skin Transcriptome of Atopic Dermatitis by Use of 1.5 mm Minipunch Biopsies

Hu, Tu; Todberg, Tanja; Ewald, David Adrian; Rosa, Joel Corrêa da; Skov, Lone; Litman, Thomas

doi:10.1016/j.jid.2022.10.004

Cited by 9 publications

(9 citation statements)

References 47 publications

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“…In addition, an important limitation is the fact that a difference in anatomical site and skin layers of the skin biopsies between VHE and AD can contribute to variation in gene expression. 40 Whole-skin biopsies of the upper extremities or trunk in the AD study were analysed, 6 whereas in the VHE study only epidermal palmar skin was analysed. 5 A previous study concluded that AD skin biopsies of the palms show transcriptional differences with biopsies of non-palmar skin, with the largest variation for hair-specific genes (absence in palmar skin) and keratin genes (unique expression of KRT9, SPINK9 and HRNR only in palmar skin).…”

Section: Discussionmentioning

confidence: 99%

“…One of the limitations of our study is the smaller sample size of the VHE dataset compared to the AD dataset, which might have resulted in less power and thus a lower number of DEGs in VHE. In addition, an important limitation is the fact that a difference in anatomical site and skin layers of the skin biopsies between VHE and AD can contribute to variation in gene expression 40 . Whole‐skin biopsies of the upper extremities or trunk in the AD study were analysed, 6 whereas in the VHE study only epidermal palmar skin was analysed 5 .…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional differences between vesicular hand eczema and atopic dermatitis

Rosenberg,

Wardenaar,

Voorberg

et al. 2023

Contact Dermatitis

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BackgroundTranscriptome analyses of vesicular hand eczema (VHE) indicated a large overlap with atopic dermatitis (AD). However, differentially expressed genes (DEGs) that differentiate VHE from AD are unknown.ObjectiveTo identify distinctive transcriptional features of VHE in comparison to AD.MethodsWe re‐analysed RNA sequencing data of 10 lesional palmar VHE epidermal biopsies and performed DEG analyses. We adjusted the obtained DEG results of 57 lesional whole AD skin biopsies of the upper extremities or trunk to our criteria. Up‐ and down‐regulated DEGs in both skin diseases, VHE‐only, AD‐only, and opposite regulated DEGs were identified. Enrichment analyses and Chi‐squared tests were conducted to test for differences in gene set enrichment between both skin diseases.ResultsComparing 3028 DEGs in VHE (1645 up; 1383 down) with 5391 DEGs in AD (3842 up; 1549 down), revealed 1516 shared DEGs (1179 up; 337 down) and 1512 DEGs unique to VHE (466 up, 1046 down). Interferon signalling and necroptosis were significantly more prominent in VHE compared to AD. Downregulated genes identified only in VHE (like DNASE1L2, KRT2, KRT9 and KRT25) indicate an aberrant epidermal differentiation.ConclusionOur study indicates a common pathophysiology between VHE and AD, but also reveals transcriptional differences between VHE and AD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptional differences between vesicular hand eczema and atopic dermatitis

Rosenberg,

Wardenaar,

Voorberg

et al. 2023

Contact Dermatitis

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“…Interestingly, we found downregulation of UGT3A in LS skin from the high AD risk patient group. We previously reported UGT3A to have the highest fraction of variance explained by AD among all genes for the same population cohort (Hu et al, 2022). UGT3A has been proposed to maintain skin homeostasis, but its biochemical mechanism in skin physiology has not yet been elucidated.…”

Section: Patients With Higher Ad Genetic Risk Were Characterized By A...mentioning

confidence: 97%

“…In total, the expression of 14759 genes (including both protein coding and non-coding genes, expressed with a mean of more than 3 counts per million (cpm) across all samples) from 148 samples were used for the analysis. Details of sample collection and data curation were reported previously (Hu et al, 2022).…”

Section: Skin Transcriptome Datamentioning

confidence: 99%

“…In the GENtofte Atopic Dermatitis (GENAD) cohort, we performed genomic, skin transcriptomic, and extensive clinical measurement on all AD and healthy control (HC) subjects, hereby generating an AD disease signature, consisting of many genes associated with activated inflammatory response and skin barrier perturbations (Hu et al, 2022). In the current study, we intend to integrate the genomic and the skin transcriptomic measurement from the same patient group to identify unique skin transcriptome features associated with AD genetic risk, and potentially, reveal the genome regulatory mechanisms in AD.…”

Section: Introductionmentioning

confidence: 99%

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An Integrated Genomic and Transcriptomic Analysis Reveals Distinct Molecular Features Associated with Mild-to-moderate Atopic Dermatitis

Todberg

Skov

et al. 2023

Preprint

Self Cite

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Atopic dermatitis (AD) is a common skin disorder, characterized by impaired skin barrier function and cutaneous inflammation. The pathophysiology of AD is incompletely understood, and has considerable genetic contributions. To obtain a detailed molecular understanding of AD, we integrated the genomic, skin transcriptomic, and clinical measurements from 30 AD and 30 healthy control (HC) subjects. We found that the AD group had mild-to-moderate disease severity and only showed slightly increased genetic risk compared with HC. When comparing within the AD group, we found that the lesional skin of patients with increased genetic risk was characterized by a possible "self-protection" mechanism, including elevation of the anti-inflammatory cytokine IL-34, activation of fibroblasts, wound healing, and the complement system. We hypothesize that this mechanism may contribute to halting further progression of AD.

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Single‐cell transcriptomics reveals prominent expression of IL‐14, IL‐18, and IL‐32 in psoriasis

Frost,

Schmidt,

Klein

et al. 2023

Eur J Immunol

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RationalePsoriasis is a chronic inflammatory skin disease involving different cytokines and chemokines.ObjectivesHere we use single‐cell transcriptomic analyses to identify relevant immune cell and non‐immune cell populations for an in‐depth characterization of cell types and inflammatory mediators in this disease.MethodsPsoriasis skin lesions of 8 patients are analyzed using single‐cell technology. Data are further validated by in situ hybridization (ISH) of human tissues, serum analyses of human samples and tissues of a murine model of psoriasis, and by in vitro cell culture experiments.ResultsSeveral different immune‐activated cell types with particular cytokine patterns are identified such as keratinocytes, T helper cells, dendritic cells, macrophages and fibroblasts. Apart from well‐known factors, IL‐14 (TXLNA), IL‐18 and IL‐32 are identified with prominent expression in individual cell types in psoriasis. The percentage of inflammatory cellular subtypes expressing IL‐14, IL‐18 and IL‐32 was significantly higher in psoriatic skin compared to healthy control skin. These findings were confirmed by ISH of human skin samples, in a murine model of psoriasis, in human serum samples and in in vitro experiments.ConclusionsTaken together, we provide a differentiated view of psoriasis immune‐cell phenotypes that support a role of IL‐14, IL‐18 and IL‐32 in psoriasis pathogenesis.This article is protected by copyright. All rights reserved

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Assessment of Spatial and Temporal Variation in the Skin Transcriptome of Atopic Dermatitis by Use of 1.5 mm Minipunch Biopsies

Cited by 9 publications

References 47 publications

Transcriptional differences between vesicular hand eczema and atopic dermatitis

Transcriptional differences between vesicular hand eczema and atopic dermatitis

An Integrated Genomic and Transcriptomic Analysis Reveals Distinct Molecular Features Associated with Mild-to-moderate Atopic Dermatitis

Single‐cell transcriptomics reveals prominent expression of IL‐14, IL‐18, and IL‐32 in psoriasis

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