RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.

RNA-seq and flow-cytometry of conventional, scalp, and palmoplantar psoriasis reveal shared and distinct molecular pathways.
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DOI:
10.1038/s41598-018-29472-w
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发表时间:
2018-07-27
期刊:
影响因子:
4.6
通讯作者:
Liao W
Liao W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ahn R;Yan D;Chang HW;Lee K;Bhattarai S;Huang ZM;Nakamura M;Singh R;Afifi L;Taravati K;Munoz-Sandoval P;Pauli M;Rosenblum MD;Liao W

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长期以来,人们认识到解剖位置是确定斑块状银屑病不同亚型的重要特征。然而,人们对头皮、掌跖和传统斑块状银屑病之间的分子差异知之甚少。为了研究这些银屑病亚型的分子异质性,我们对头皮、掌跖和传统斑块状银屑病患者的皮肤样本沿着健康对照患者的样本进行了RNA-seq和流式细胞术。我们使用加权基因共表达网络分析(WGCNA)进行差异表达分析和网络分析。我们的分析揭示了一组核心的763个差异表达基因共同的所有亚型银屑病。相比之下,我们确定了605,632和262个基因独特的差异表达在传统的,头皮,掌跖银屑病,分别。WGCNA和途径分析揭示了核心基因以及亚型特异性基因的生物学过程。流式细胞术分析显示,与对照组相比,所有银屑病亚型中CD 4 + T调节细胞的百分比均增加,而不同的银屑病亚型在IL-17 A、IFN-γ和IL-22产生方面存在差异。这项工作揭示了斑块状银屑病的分子异质性,并确定了亚型特异性信号通路,这将有助于开发适合于斑块状银屑病每种亚型的治疗方法。
It has long been recognized that anatomic location is an important feature for defining distinct subtypes of plaque psoriasis. However, little is known about the molecular differences between scalp, palmoplantar, and conventional plaque psoriasis. To investigate the molecular heterogeneity of these psoriasis subtypes, we performed RNA-seq and flow cytometry on skin samples from individuals with scalp, palmoplantar, and conventional plaque psoriasis, along with samples from healthy control patients. We performed differential expression analysis and network analysis using weighted gene coexpression network analysis (WGCNA). Our analysis revealed a core set of 763 differentially expressed genes common to all sub-types of psoriasis. In contrast, we identified 605, 632, and 262 genes uniquely differentially expressed in conventional, scalp, and palmoplantar psoriasis, respectively. WGCNA and pathway analysis revealed biological processes for the core genes as well as subtype-specific genes. Flow cytometry analysis revealed a shared increase in the percentage of CD4+ T regulatory cells in all psoriasis subtypes relative to controls, whereas distinct psoriasis subtypes displayed differences in IL-17A, IFN-gamma, and IL-22 production. This work reveals the molecular heterogeneity of plaque psoriasis and identifies subtype-specific signaling pathways that will aid in the development of therapy that is appropriate for each subtype of plaque psoriasis.
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