Incomplete differentiation of fetal keratinocytes in the skin equivalent leads to the default pathway of apoptosis.
Incomplete differentiation of fetal keratinocytes in the skin equivalent leads to the default pathway of apoptosis.
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皮肤等价物中胎儿角质形成细胞的不完全分化导致默认的细胞凋亡途径。
DOI：
10.1006/excr.1996.3441
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发表时间：
1997
影响因子：
3.7
通讯作者：
Cooklis,M
中科院分区：
文献类型：
--
作者：
Haake,AR;Cooklis,M
人胚胎皮肤在发育过程中，表皮的形态发生和分化程序发生了巨大的变化。在早期阶段源自胎儿基底细胞的角质形成细胞仅经历不完全的角质化，并且最终被新形成的胎儿角质形成细胞所取代，所述新形成的胎儿角质形成细胞完成终末分化程序并形成第一颗粒层和角质层。一旦建立，这个程序在整个生命中不断重复，因为表皮不断更新。为了测试早期胎儿角质形成细胞的发育潜力，我们培养了他们在生理皮肤等效（SE）系统中存在不同的视黄酸（RA）浓度，并将其与相同条件下培养的新生儿角质形成细胞进行了比较。胎儿和新生儿SE的反应已经通过分析表皮形态、RA反应性和分化特异性角蛋白和聚丝蛋白的存在和分布、增殖和凋亡来表征。我们的研究表明，胎儿基底角质形成细胞已经被编程形成颗粒层和不完整的角质层，即使从这些层形成之前的阶段分离出来。胎儿角质形成细胞与新生儿角质形成细胞在调节表皮形态和分化标志物表达方面对RA的反应不同。RA-响应K1和K19的调制发生在胎儿SE和新生儿SE，但胎儿角质形成细胞在培养基中较低的RA浓度响应。相比之下，胎儿角质形成细胞似乎比新生儿角质形成细胞在丝聚蛋白表达和角质层形成方面的反应性更低。这些分化和体外RA反应的差异可能与胎儿和新生儿角质形成细胞在RA信号通路中的固有阶段特异性差异有关，包括维甲酸受体RARβ的表达。此外，胎儿SE中的高凋亡率表明凋亡是在没有完全角质形成细胞分化的情况下采取的默认途径。
The program of epidermal morphogenesis and differentiation changes dramatically during development of human fetal skin. Keratinocytes derived from fetal basal cells at early stages undergo only an incomplete keratinization and are eventually replaced by newly formed fetal keratinocytes that complete the terminal differentiation program and form the first stratum granulosum and stratum corneum. Once established, this program is reiterated throughout life, as the epidermis continually renews. To test the developmental potential of early fetal keratinocytes, we have cultured them in the physiologic skin equivalent (SE) system in the presence of varied retinoic acid (RA) concentrations and have compared them to neonatal keratinocytes cultured under the same conditions. The responses of fetal and neonatal SEs have been characterized by analysis of epidermal morphology, the presence and distribution of RA-responsive and differentiation-specific keratins and filaggrin, proliferation, and apoptosis. Our study shows that fetal basal keratinocytes already are programmed to form the granular layer and incomplete stratum corneum, even when isolated from a stage prior to formation of these layers. Fetal keratinocytes respond differently than neonatal keratinocytes to RA in terms of modulation of both epidermal morphology and expression of differentiation markers. Modulation of RA-responsive K1 and K19 occurs in both fetal SE and neonatal SE but the fetal keratinocyte responds at lower RA concentrations in the medium. In contrast, fetal keratinocytes appear to be less responsive than neonatal keratinocytes in terms of filaggrin expression and stratum corneum formation. These differences in the differentiation and RA responsein vitromay be related to inherent stage-specific differences between fetal and neonatal keratinocytes in RA-signaling pathways including expression of the retinoic acid receptor, RARβ. Furthermore, high rates of apoptosis in the fetal SE suggest that apoptosis is the default pathway that is taken in the absence of complete keratinocyte differentiation.