Artificial induction and disease-related conversion of the hepatic fate
Artificial induction and disease-related conversion of the hepatic fate
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DOI：
10.1016/j.gde.2013.04.006
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发表时间：
2013-10-01
影响因子：
4
通讯作者：
Suzuki, Atsushi
中科院分区：
文献类型：
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作者：
Suzuki, Atsushi
在正常的生理条件下，细胞的命运。组成器官的各个部分是在发育过程中确定的，并且永远不会改变为其他细胞类型。然而，最近在诱导细胞重编程方面的进展提供了通过人工调节细胞的微环境或基因表达模式从原始细胞来源产生完全不同的细胞类型的机会。虽然肝细胞通常仅存在于肝脏中，但可以通过表达确定的外源性转录因子在皮肤来源的成纤维细胞中诱导肝程序。这些诱导的肝细胞样细胞具有肝细胞特异性，并在移植后功能上恢复受损的肝组织。另一方面，肝细胞本身可以转化为胆系细胞，作为肝病的致病因素。因此，阻断这种疾病相关的肝脏命运重编程将成为肝脏难治性疾病的新治疗策略。此外，肝细胞可以通过表达胰腺发育所需的转录因子来部分接受胰腺程序，这表明胰岛素产生细胞可以从肝细胞产生并用于治疗糖尿病。上述进展将促进对肝细胞特性和可塑性的分子本质的研究，并有助于开发潜在的肝脏疾病治疗方法。
Under normal physiological conditions, the fates of cells that. compose various parts of organs are determined during development, and never change to those of other cell types. However, recent advances in induction of cellular reprogramming provide chances to generate a completely different cell type from an original cell source by artificially modulating the microenvironments or gene expressions pattern of cells. Although hepatocytes normally only reside in the liver, the hepatic program can be induced in skin-derived fibroblasts by expressing defined extrinsic transcription factors. These induced hepatocyte-like cells have hepatocyte-specific properties and functionally restore damaged hepatic tissues after transplantation. On the other hand, hepatocytes themselves can be converted into biliary lineage cells as a causative factor of hepatic diseases. Thus, blockade of such disease-related reprogramming of the hepatic fate will become a new therapeutic strategy for refractory diseases in the liver. Moreover, hepatocytes could partially accept the pancreatic program by expressing transcription factors required for pancreas development, suggesting that insulin-producing cells could be generated from hepatocytes and used to treat diabetes. The above-mentioned progress will stimulate studies on the molecular nature of cellular identity and plasticity in hepatocytes, and contribute to the development of potential therapies for liver diseases.