Yuan S, Rosenberg L, Paraskevas S, Agapitos D, Duguid W P
Department of Pathology, McGill University, Montreal, Canada.
Differentiation. 1996 Oct;61(1):67-75. doi: 10.1046/j.1432-0436.1996.6110067.x.
Transdifferentiation is a change from one differentiated phenotype to another, involving morphological and functional phenotypic markers. Stability of the cellular phenotype is probably related to the extracellular milieu, as well as cytoplasmic and nuclear components that interact to control gene expression, and the conversion of cell phenotype is likely to be accomplished by selective enhancement of gene expression, which controls the terminal developmental commitment of cells. In this paper, we show the induction of cultured human islets cells to alter their usual phenotypic expression and attain morphological and functional characteristics of duct cells. Islets were isolated by collagenase digestion of pancreata that were removed from cadaveric organ donors. The islets were purified on a two-step density gradient of bovine serum albumin and were then placed into a three-dimensional rat-tail collagen gel matrix supplemented with NuSerum epithelial growth factor and cholera toxin. During the initial 96 h of culture, the islets underwent a cystic transformation that was associated with (1) the maintenance of immunoreactivity for neuron-specific enolase, an endocrine cell marker, but a progressive loss of insulin gene expression, (2) a loss of immunoreactivity for insulin protein, and (3) the appearance of CK-19, a marker for ductal cells. After the transformation was complete, the cells had the ultrastructural appearance of primitive duct-like cells. Cyst enlargement after the initial 96 h was associated, at least in part, with cell replication, as reflected in the 1500% increase in the incorporation of tritiated thymidine. These experiments are consistent with the transdifferentiation of an islet cell to a ductal cell. The exact mechanisms involved still need to be fully elucidated.
转分化是指从一种分化表型转变为另一种分化表型，涉及形态学和功能表型标志物。细胞表型的稳定性可能与细胞外环境以及相互作用以控制基因表达的细胞质和细胞核成分有关，而细胞表型的转变可能是通过基因表达的选择性增强来实现的，基因表达控制着细胞的终末发育命运。在本文中，我们展示了培养的人胰岛细胞可被诱导改变其通常的表型表达，并获得导管细胞的形态学和功能特征。通过胶原酶消化从尸体器官供体获取的胰腺来分离胰岛。将胰岛在牛血清白蛋白的两步密度梯度上进行纯化，然后置于补充有新生牛血清、上皮生长因子和霍乱毒素的三维大鼠尾胶原凝胶基质中。在培养的最初96小时内，胰岛经历了囊性转变，这与以下情况相关：（1）维持对神经元特异性烯醇化酶（一种内分泌细胞标志物）的免疫反应性，但胰岛素基因表达逐渐丧失；（2）胰岛素蛋白免疫反应性丧失；（3）出现导管细胞标志物细胞角蛋白19（CK-19）。转变完成后，细胞具有原始导管样细胞的超微结构外观。最初96小时后囊肿增大至少部分与细胞复制有关，这反映在氚标记胸腺嘧啶掺入量增加了1500%。这些实验与胰岛细胞向导管细胞的转分化一致。其中确切的机制仍需充分阐明。
