Sun Xiaoyun, Kim Arianna, Nakatani Masashi, Shen Yao, Liu Liang
JP Sulzberger Columbia Genome Center, Columbia University, New York, NY, USA.
Department of Dermatology, Columbia University, New York, NY, USA.
Exp Dermatol. 2016 Sep;25(9):708-13. doi: 10.1111/exd.13057. Epub 2016 Jun 30.
Solar ultraviolet radiation (UVR) is the major risk factor for skin carcinogenesis. To gain new insights into the molecular pathways mediating UVR effects in the skin, we performed comprehensive transcriptomic analyses to identify shared and distinctive molecular responses to UVR between human keratinocytes and melanocytes. Keratinocytes and melanocytes were irradiated with varying doses of UVB (10, 20 and 30 mJ/cm(2) ) then analysed by RNA-Seq at different time points post-UVB radiation (4, 24 and 72 h). Under basal conditions, keratinocytes and melanocytes expressed similar number of genes, although they each expressed a distinctive subset of genes pertaining to their specific cellular identity. Upon UVB radiation, keratinocytes displayed a clear pattern of time- and dose-dependent changes in gene expression that was different from melanocytes. The early UVB-responsive gene set (4 h post-UVR) differed significantly from delayed UVB-responsive gene sets (24 and 72 h). We also identified multiple novel UVB signature genes including PRSS23, SERPINH1, LCE3D and CNFN, which were conserved between melanocyte and keratinocyte lines from different individuals. Taken together, our findings elucidated both common and distinctive molecular features between melanocytes and keratinocytes and uncovered novel UVB signature genes that might be utilized to predict UVB photobiological effects on the skin.
太阳紫外线辐射(UVR)是皮肤癌发生的主要风险因素。为了深入了解介导UVR对皮肤影响的分子途径,我们进行了全面的转录组分析,以确定人类角质形成细胞和黑素细胞对UVR的共同和独特分子反应。用不同剂量的UVB(10、20和30 mJ/cm²)照射角质形成细胞和黑素细胞,然后在UVB辐射后的不同时间点(4、24和72小时)通过RNA测序进行分析。在基础条件下,角质形成细胞和黑素细胞表达的基因数量相似,尽管它们各自表达了与其特定细胞身份相关的独特基因子集。UVB辐射后,角质形成细胞在基因表达上呈现出与黑素细胞不同的明显的时间和剂量依赖性变化模式。早期UVB反应基因集(UVR后4小时)与延迟UVB反应基因集(24和72小时)有显著差异。我们还鉴定了多个新的UVB特征基因,包括PRSS23、SERPINH1、LCE3D和CNFN,这些基因在来自不同个体的黑素细胞和角质形成细胞系中是保守的。综上所述,我们的研究结果阐明了黑素细胞和角质形成细胞之间的共同和独特分子特征,并发现了可能用于预测UVB对皮肤光生物学效应的新的UVB特征基因。