Keratinocyte Detachment-Differentiation Connection Revisited, or Anoikis-Pityriasi Nexus Redux
Keratinocyte Detachment-Differentiation Connection Revisited, or Anoikis-Pityriasi Nexus Redux
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DOI：
10.1371/journal.pone.0100279
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发表时间：
2014-06-24
期刊：
影响因子：
3.7
通讯作者：
Blumenberg, Miroslav
中科院分区：
文献类型：
--
作者：
Banno, Tomohiro;Blumenberg, Miroslav
表皮是一个不断自我更新和分化的器官，它产生保护性角质层，保护我们免受外部化学、物理和微生物的威胁。表皮分化是一个受多种影响调节的多步骤过程，其中一些影响未知，另一些尚未充分探索。角质形成细胞从基底膜脱离就是这样一种促分化刺激物。在这里，我们定义了分化过程中的转录变化，特别是由与基质分离引起的转录变化。使用全面的转录分析，我们重新审视了分离作为角质形成细胞分化信号的影响。我们确定了受分离调节的基因、相应的本体论类别，并使用荟萃分析将这些基因和类别与其他促分化刺激调节的基因和类别进行了比较。我们鉴定了悬浮角质形成细胞中过表达的 762 个基因，包括已知和新的分化标记物，以及贴壁细胞中的 1427 个基因，包括基底层标记物。脱离诱导表皮发育、角化和桥粒基因，还有先天免疫、增殖抑制剂、转录调节因子和 MAPK；相反，贴壁细胞过度表达细胞周期、锚定、运动、剪接和线粒体基因，以及细胞凋亡的正向和负向调节因子。荟萃分析确定了哪些脱离调节类别与体内基底上位置、体外达到汇合以及抑制 JUN 激酶诱导的类别重叠。附着的基底细胞和体内基底细胞都过度表达线粒体成分。有趣的是，黑素体运输成分也在附着的和体内的基底角质形成细胞中过度表达。这些结果表明，特定的促分化信号诱导角化过程的特定特征，这些特征在体内协调成和谐的表皮稳态。
Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis.