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转录组学揭示了两种人类特应性皮炎小鼠模型的转化价值。

Transcriptomic insight into the translational value of two murine models in human atopic dermatitis.

机构信息

Department of Physiology, College of Medicine, Chung-Ang University, Seoul, 06974, Korea.

Department of Physiology, School of Medicine, Jeju National University, Jeju, 63243, Korea.

出版信息

Sci Rep. 2021 Mar 23;11(1):6616. doi: 10.1038/s41598-021-86049-w.

DOI:10.1038/s41598-021-86049-w
PMID:33758305
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7988112/
Abstract

This study sought to develop a novel diagnostic tool for atopic dermatitis (AD). Mouse transcriptome data were obtained via RNA-sequencing of dorsal skin tissues of CBA/J mice affected with contact hypersensitivity (induced by treatment with 1-chloro-2,4-dinitrobenzene) or brush stimulation-induced AD-like skin condition. Human transcriptome data were collected from German, Swedish, and American cohorts of AD patients from the Gene Expression Omnibus database. edgeR and SAM algorithms were used to analyze differentially expressed murine and human genes, respectively. The FAIME algorithm was then employed to assign pathway scores based on KEGG pathway database annotations. Numerous genes and pathways demonstrated similar dysregulation patterns in both the murine models and human AD. Upon integrating transcriptome information from both murine and human data, we identified 36 commonly dysregulated differentially expressed genes, which were designated as a 36-gene signature. A severity score (AD index) was applied to each human sample to assess the predictive power of the 36-gene AD signature. The diagnostic power and predictive accuracy of this signature were demonstrated for both AD severity and treatment outcomes in patients with AD. This genetic signature is expected to improve both AD diagnosis and targeted preclinical research.

摘要

本研究旨在开发一种新型的特应性皮炎(AD)诊断工具。通过对接触过敏(用 1-氯-2,4-二硝基苯处理诱导)或刷子刺激诱导的 AD 样皮肤状况的 CBA/J 小鼠背部皮肤组织进行 RNA-seq,获得了小鼠转录组数据。人类转录组数据来自德国、瑞典和美国 AD 患者的 Gene Expression Omnibus 数据库。edgeR 和 SAM 算法分别用于分析差异表达的小鼠和人类基因。然后使用 FAIME 算法根据 KEGG 途径数据库注释为途径评分。在小鼠模型和人类 AD 中,许多基因和途径表现出相似的失调模式。在整合来自小鼠和人类数据的转录组信息后,我们确定了 36 个共同失调的差异表达基因,将其命名为 36 基因特征。对每个人类样本应用严重程度评分(AD 指数)来评估 36 基因 AD 特征的预测能力。该特征对 AD 严重程度和 AD 患者的治疗结果均具有诊断能力和预测准确性。该遗传特征有望改善 AD 的诊断和靶向临床前研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/3591fbf16b18/41598_2021_86049_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/13b732f8f084/41598_2021_86049_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/605ac4d652e1/41598_2021_86049_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/df3996633539/41598_2021_86049_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/3591fbf16b18/41598_2021_86049_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/13b732f8f084/41598_2021_86049_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/605ac4d652e1/41598_2021_86049_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/df3996633539/41598_2021_86049_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ba/7988112/3591fbf16b18/41598_2021_86049_Fig4_HTML.jpg

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本文引用的文献

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Nucleic Acids Res. 2021 Jan 8;49(D1):D545-D551. doi: 10.1093/nar/gkaa970.
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Enhanced Thermal Sensitivity of TRPV3 in Keratinocytes Underlies Heat-Induced Pruritogen Release and Pruritus in Atopic Dermatitis.角质形成细胞中 TRPV3 的热敏感性增强是特应性皮炎中热诱导致痒原释放和瘙痒的基础。
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Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma.
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CRISPR 诱导的 TRPA1 基因敲除大鼠在疼痛、瘙痒和哮喘模型中的行为特征。
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Toward understanding the origin and evolution of cellular organisms.为了理解细胞生物的起源和进化。
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Early-onset pediatric atopic dermatitis is characterized by T2/T17/T22-centered inflammation and lipid alterations.早发性儿童特应性皮炎的特征是 T2/T17/T22 为中心的炎症和脂质改变。
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Expression of keratin 1, keratin 10, desmoglein 1 and desmocollin 1 in the epidermis: possible downregulation by interleukin-4 and interleukin-13 in atopic dermatitis.角蛋白 1、角蛋白 10、桥粒芯糖蛋白 1 和桥粒胶蛋白 1 在表皮中的表达:特应性皮炎中白细胞介素-4 和白细胞介素-13 可能下调。
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