Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation
Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation
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DOI：
10.1016/j.yexcr.2018.05.031
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发表时间：
2018-08-15
影响因子：
3.7
通讯作者：
Southgate, Jennifer
中科院分区：
文献类型：
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作者：
Hustler, Arianna;Eardley, Ian;Southgate, Jennifer
鉴定分化细胞表达的转录因子不仅能提供组织特异性途径的信息，而且有助于鉴定细胞重编程的主调节因子。如果应用，这种方法可以产生健康的自体组织特异性细胞用于临床使用，其中来自同源组织的细胞由于疾病而不可用。正常人口腔上皮细胞和尿路上皮细胞的衍生保持在相同的培养条件下，缺乏显着的指导性或许可的信号线索被发现显示固有的相似性和差异的表型。对参与驱动尿路上皮型分化的转录因子的研究显示，颊上皮细胞中PPARG、GATA 3和FOXA 1基因的表达最少或不表达。颊上皮细胞中GATA3或PPARy 1的蛋白编码序列的逆转录病毒过表达导致相应蛋白的核免疫定位，两种转导也诱导尿路上皮分化相关的紧密连接蛋白3紧密连接蛋白的表达。PPARG1过表达单独夹带核FOXA 1和GATA 3蛋白的表达，提供了其在转录因子网络中的上游定位的客观证据，并将其鉴定为尿路上皮型转分化或重编程的候选因子。
Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signaling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of protein coding sequences for GATA3 or PPARy1 in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARG1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming.