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Hierarchical transcriptional profile of urothelial cells development and differentiation

机译:尿检细胞发育和分化的分层转录谱

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The urothelial lining of the lower urinary tract is the most efficient permeability barrier in animals, exhibiting a highly differentiated phenotype and a remarkable regenerative capacity upon wounding. During development and possibly during repair, cells undergo a sequence of hierarchical transcriptional events that mark the transition of these cells from the least differentiated urothelial phenotype characteristic of the basal cell layer, to the most differentiated cellular phenotype characteristic of the superficial cell layer. Unraveling normal urothelial differentiation program is essential to uncover the underlying causes of many congenital abnormalities and for the development of an appropriate differentiation niche for stem cells, for future use in urinary tract tissue engineering and organ reconstruction. Kruppel like factor-5 appears to be at the top of the hierarchy activating several downstream transcription factors, the most prominent of which is peroxisome proliferator activator receptor-y. Eventually those lead to the activation of transcription factors that directly regulate the expression of uroplakin proteins along with other proteins that mediate the permeability function of the urothelium.
机译:下尿路的尿路上皮衬里是动物体内最有效的通透性屏障,在受伤时表现出高度分化的表型和显著的再生能力。在发育过程中,可能在修复过程中,细胞经历一系列分级转录事件,这些事件标志着这些细胞从基底细胞层分化最差的尿路上皮表型特征过渡到表层细胞层分化最差的细胞表型特征。解开正常的尿路上皮分化程序对于揭示许多先天性异常的潜在原因以及为干细胞开发合适的分化生态位至关重要,以备将来用于尿路组织工程和器官重建。Kruppel样因子-5似乎位于激活几个下游转录因子的层次结构的顶部,其中最突出的是过氧化物酶体增殖物激活物受体-y。最终,它们导致转录因子的激活,这些转录因子与其他调节尿路上皮通透性功能的蛋白质一起直接调节尿路板蛋白的表达。

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