Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor.,Acta Pharmacologica Sinica

当前位置： X-MOL 学术 › Acta Pharmacol. Sin. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Chemical cocktails enable hepatic reprogramming of human urine-derived cells with a single transcription factor.
Acta Pharmacologica Sinica ( IF 6.9 ) Pub Date : 2018-10-12 , DOI: 10.1038/s41401-018-0170-z
Wei Tang _{1,

2} , Ren Guo _{2,

3} , Shi-Jun Shen ₁ , Yang Zheng _{2,

3,

4} , Yu-Ting Lu _{3,

4,

5} , Meng-Meng Jiang _{2,

3,

4} , Xue Cui _{1,

2} , Ci-Zhong Jiang ₁ , Xin Xie _{1,

2,

5,

6}

Affiliation

Human liver or hepatocyte transplantation is limited by a severe shortage of donor organs. Direct reprogramming of other adult cells into hepatic cells may offer a solution to this problem. In a previous study, we have generated hepatocyte-like cells from mouse fibroblasts using only one transcription factor (TF) plus a chemical cocktail. Here, we show that human urine-derived epithelial-like cells (hUCs) can also be transdifferentiated into human hepatocyte-like cells (hiHeps) using one TF (Foxa3, Hnf1α, or Hnf4α) plus the same chemical cocktail CRVPTD (C, CHIR99021; R, RepSox; V, VPA; P, Parnate; T, TTNPB; and D, Dznep). These hiHeps express multiple hepatocyte-specific genes and display functions characteristic of mature hepatocytes. With the introduction of the large T antigen, these hiHeps can be expanded in vitro and can restore liver function in mice with concanavalin-A-induced acute liver failure. Our study provides a strategy to generate functional hepatocyte-like cells from hUCs by using a single TF plus a chemical cocktail.

中文翻译：

化学鸡尾酒能够使用单一转录因子对人类尿液来源的细胞进行肝脏重编程。

人类肝脏或肝细胞移植受到供体器官严重短缺的限制。将其他成体细胞直接重编程为肝细胞可能会解决这个问题。在之前的一项研究中，我们仅使用一种转录因子 (TF) 和一种化学混合物从小鼠成纤维细胞中生成了肝细胞样细胞。在这里，我们展示了使用一种 TF（Foxa3、Hnf1α 或 Hnf4α）加上相同的化学混合物 CRVPTD（C，CHIR99021 ；R，RepSox；V，VPA；P，Parnate；T，TTNPB；和 D，Dznep）。这些 hiHeps 表达多个肝细胞特异性基因并显示成熟肝细胞的功能特征。随着大T抗原的引入，这些 hiHeps 可以在体外扩增，并可以恢复伴刀豆球蛋白 A 诱导的急性肝衰竭小鼠的肝功能。我们的研究提供了一种策略，通过使用单个 TF 和化学混合物从 hUCs 生成功能性肝细胞样细胞。

更新日期：2019-01-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11