A Comprehensive Analysis of MicroRNA Expression During Human Keratinocyte Differentiation In Vitro and In Vivo

A Comprehensive Analysis of MicroRNA Expression During Human Keratinocyte Differentiation In Vitro and In Vivo
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DOI:
10.1038/jid.2010.268
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发表时间:
2011-01-01
影响因子:
6.5
通讯作者:
Knott, Anja
Knott, Anja
中科院分区:
医学1区
文献类型:
--
作者:
Hildebrand, Janosch;Ruetze, Martin;Knott, Anja

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在这里,我们报告了一个全面的调查中的微小RNA(miRNA)表达谱的变化对人角质形成细胞(HK)分化在体外和体内。我们已经监测了377个miRNA在钙诱导的原发性HK分化过程中的表达模式,并将这些模式与表皮干细胞、瞬时扩增细胞和人类皮肤终末分化HK的miRNA表达谱进行了比较。除了先前描述的miR-203之外,我们还发现了另外9种与体外和体内HK分化相关的miRNA(miR-23 b、miR-95、miR-210、miR-224、miR-26 a、miR-200 a、miR-27 b、miR-328和miR-376 a)。原位杂交实验证实miR-23 b是HK体内分化的标志物。此外,使用3 '-非翻译区-荧光素酶测定对预测的miRNA靶进行的基因本体分析和功能验证表明,在HK分化中上调的多种miRNA在皮肤发育期间协同调节基因表达。因此,我们的研究结果为进一步分析表皮分化过程中miRNA的功能提供了基础。
Here, we report a comprehensive investigation of changes in microRNA (miRNA) expression profiles on human keratinocyte (HK) differentiation in vitro and in vivo. We have monitored expression patterns of 377 miRNAs during calcium-induced differentiation of primary HKs, and have compared these patterns with miRNA expression profiles of epidermal stem cells, transient amplifying cells, and terminally differentiated HKs from human skin. Apart from the previously described miR-203, we found an additional nine miRNAs (miR-23b, miR-95, miR-210, miR-224, miR-26a, miR-200a, miR-27b, miR-328, and miR-376a) that are associated with HK differentiation in vitro and in vivo. In situ hybridization experiments confirmed miR-23b as a marker of HK differentiation in vivo. Additionally, gene ontology analysis and functional validation of predicted miRNA targets using 3'-untranslated region-luciferase assays suggest that multiple miRNAs that are upregulated on HK differentiation cooperate to regulate gene expression during skin development. Our results thus provide the basis for further analysis of miRNA functions during epidermal differentiation.