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细胞命运转变:直接诱导成纤维细胞为肝细胞样细胞。

Cell fate conversion: direct induction of hepatocyte-like cells from fibroblasts.

机构信息

State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Yueyang Road 320, Shanghai 200031, China.

出版信息

J Cell Biochem. 2013 Feb;114(2):256-65. doi: 10.1002/jcb.24380.

Abstract

One of the essential features of stem cells is their cellular plasticity to differentiate into daughter cells with defined functions. Recently, induction of pluripotent stem cells from somatic cells by defined transcription factors led to the focus on cellular plasticity of terminally differentiated cells. This approach is adopted by other studies to demonstrate the cell fate conversion between different lineages of terminally differentiated cells. We and others showed that induced hepatocyte-like (iHep) cells are directly converted from mouse fibroblasts by overexpression of liver-enriched transcription factors. iHep cells as well as pluripotent stem cell- or mesenchymal stem cell-derived hepatocyte-like cells provide potential cell sources for disease modeling, transplantation, and tissue engineering independent of donor organs. Here, we review the latest advances in generating hepatocyte-like cells and summarize general criteria for evaluating these cells. In addition, we propose a possible role of the p19(Arf) /p53 pathway in cell fate maintenance, which apparently limits the formation of induced pluripotent stem (iPS) cells and iHep cells.

摘要

干细胞的一个重要特征是其细胞可塑性,可以分化为具有特定功能的子细胞。最近,通过定义转录因子将体细胞诱导为多能干细胞,这使得人们关注终末分化细胞的细胞可塑性。其他研究也采用这种方法来证明不同终末分化细胞谱系之间的细胞命运转换。我们和其他人表明,通过过表达肝富集转录因子,诱导的肝细胞样(iHep)细胞可以直接从小鼠成纤维细胞中转化而来。iHep 细胞以及多能干细胞或间充质干细胞来源的肝细胞样细胞为疾病建模、移植和组织工程提供了潜在的细胞来源,而无需供体器官。在这里,我们综述了生成肝细胞样细胞的最新进展,并总结了评估这些细胞的一般标准。此外,我们提出了 p19(Arf)/p53 通路在细胞命运维持中的可能作用,该通路显然限制了诱导多能干细胞(iPS)细胞和 iHep 细胞的形成。

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