Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis
Remodeling of Three-Dimensional Organization of the Nucleus during Terminal Keratinocyte Differentiation in the Epidermis
复制标题
DOI：
10.1038/jid.2013.66
复制
发表时间：
2013-09-01
影响因子：
6.5
通讯作者：
Botchkarev, Vladimir A.
中科院分区：
文献类型：
--
作者：
Gdula, Michal R.;Poterlowicz, Krzysztof;Botchkarev, Vladimir A.
表皮角质形成细胞（KCs）的细胞核是一个复杂且高度区室化的细胞器，其结构在终末分化和基因组从基底和棘状表皮细胞中所见的转录活性状态转变为皮质层角质化细胞中的完全失活状态期间显著改变。在这里，我们使用激光共聚焦显微镜，然后通过计算机图像分析和数学建模，证明了在正常小鼠足垫表皮中，KC从基底表皮层向颗粒层的过渡伴随着核结构和微环境的显著差异，包括：（i）核体积减少;（ii）转录活性染色质标记物表达减少;（iii）核仁数量的内化和减少;（iv）着丝粒周围异染色质簇数量的增加;以及（v）着丝粒周围簇、染色体区域3和核仁之间的关联频率的增加。这些数据表明，核仁和着丝粒周围异染色质簇作为细胞核微环境的组织者的作用，所述细胞核微环境是正确执行区分KC的基因表达程序所需的，并为进一步分析病理性皮肤病中观察到的拓扑基因组组织的改变提供了重要的背景信息，所述病理性皮肤病包括表皮分化障碍和表皮肿瘤。
The nucleus of epidermal keratinocytes (KCs) is a complex and highly compartmentalized organelle, whose structure is markedly changed during terminal differentiation and transition of the genome from a transcriptionally active state seen in the basal and spinous epidermal cells to a fully inactive state in the keratinized cells of the cornified layer. Here, using multicolor confocal microscopy, followed by computational image analysis and mathematical modeling, we demonstrate that in normal mouse footpad epidermis, transition of KCs from basal epidermal layer to the granular layer is accompanied by marked differences in nuclear architecture and microenvironment including the following: (i) decrease in the nuclear volume; (ii) decrease in expression of the markers of transcriptionally active chromatin; (iii) internalization and decrease in the number of nucleoli; (iv) increase in the number of pericentromeric heterochromatic clusters; and (v) increase in the frequency of associations between the pericentromeric clusters, chromosomal territory 3, and nucleoli. These data suggest a role for nucleoli and pericentromeric heterochromatin clusters as organizers of nuclear microenvironment required for proper execution of gene expression programs in differentiating KCs, and provide important background information for further analyses of alterations in the topological genome organization seen in pathological skin conditions, including disorders of epidermal differentiation and epidermal tumors.