Cell fate modification toward the hepatic lineage by extrinsic factors
Cell fate modification toward the hepatic lineage by extrinsic factors
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DOI：
10.1093/jb/mvx028
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发表时间：
2017-07
期刊：
影响因子：
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通讯作者：
Masaki Kawamata;A. Suzuki
中科院分区：
文献类型：
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作者：
Masaki Kawamata;A. Suzuki
通过用小分子靶向其信号网络和/或从基因上改变关键转录因子的表达，可以改变体细胞的谱系。根据因素的组合，成纤维细胞可以完全重编程为诱导多能干（iPS）细胞，或直接转化为特定的细胞谱系，绕过多能状态。明确靶细胞的产生将使需要细胞移植治疗的患者受益匪浅。自从iPS细胞首次产生以来的十年间，许多细胞类型已经由成纤维细胞通过直接转化诱导而来，包括肝细胞。转化的肝细胞样细胞已被证明在移植到小鼠肝病模型中后可以重新填充肝组织，这表明未来在人类中的应用前景。因此，为了实现安全有效的细胞移植治疗，正在开发各种产生肝细胞样细胞的方法。在这篇综述中，我们总结了当前通过使用外在因素改变细胞命运来生成肝细胞样细胞的方法。
The lineage of a somatic cell can be altered by targeting its signaling networks with small molecules and/or genetically altering the expression of key transcription factors. Depending on the combination of factors, fibroblasts can be fully reprogrammed into induced pluripotent stem (iPS) cells or directly converted into specific cell lineages, bypassing the pluripotent state. The generation of defined target cells will enormously benefit patients who require cell transplantation therapy. In the decade, since iPS cells were first generated, many cell types have been induced from fibroblasts by direct conversion, including hepatocytes. Converted hepatocyte-like cells have been shown to repopulate liver tissues after transplantation in mouse liver disease models, suggesting promise for future application in humans. Thus, to realize safe and efficient cell transplantation therapy, various methods for generating hepatocyte-like cells are being developed. In this review, we summarize the current methods for the generation of hepatocyte-like cells via cell fate modification using extrinsic factors.