Generation of metabolically functional hepatocyte-like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction.
Generation of metabolically functional hepatocyte-like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction.
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DOI：
10.1111/gtc.12814
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Kano K
中科院分区：
文献类型：
--
作者：
Hagiwara R;Oki Y;Matsumaru T;Ibayashi S;Kano K
成熟脂肪细胞来源的去分化脂肪（DFAT）细胞已被鉴定为具有与间充质干细胞相似的多能性，但将DFAT细胞转化为肝细胞的方法以前是未知的。在这里，通过对基因表达谱的全面分析，我们提取了三种可以将DFAT细胞转化为肝细胞的转录因子，即Foxa 2、Hnf 4a和Sall 1（FHS）。肝原性诱导将FHS感染的DFAT细胞转化为上皮样形态状态，并促进肝细胞特异性特征的表达。此外，DFAT衍生的肝细胞样（D-Hep）细胞催化几种化合物的解毒。这些结果表明，用通过综合基因表达分析提取的三种基因转导DFAT细胞，有效地产生了具有与原代肝细胞相似的解毒能力的D‐Hep细胞。因此，D-Hep细胞可用作替代肝细胞的新细胞来源，并可应用于药物发现研究，如肝毒性筛选和药物代谢试验。在这项研究中，我们对肝细胞、成熟脂肪细胞衍生的去分化脂肪（DFAT）细胞、肝干细胞和脂肪细胞的整体表达谱进行了全面分析，以确定三种转录因子Foxa 2、Hnf 4a和Sall 1-可以特异性诱导DFAT细胞中的肝细胞分化。
Mature adipocyte‐derived dedifferentiated fat (DFAT) cells have been identified to possess similar multipotency to mesenchymal stem cells, but a method for converting DFAT cells into hepatocytes was previously unknown. Here, using comprehensive analysis of gene expression profiles, we have extracted three transcription factors, namely Foxa2, Hnf4a and Sall1 (FHS), that can convert DFAT cells into hepatocytes. Hepatogenic induction has converted FHS‐infected DFAT cells into an epithelial‐like morphological state and promoted the expression of hepatocyte‐specific features. Furthermore, the DFAT‐derived hepatocyte‐like (D‐Hep) cells catalyzed the detoxification of several compounds. These results indicate that the transduction of DFAT cells with three genes, which were extracted by comprehensive gene expression analysis, efficiently generated D‐Hep cells with detoxification abilities similar to those of primary hepatocytes. Thus, D‐Hep cells may be useful as a new cell source for surrogate hepatocytes and may be applied to drug discovery studies, such as hepatotoxicity screening and drug metabolism tests. In this study, we used a comprehensive analysis of the global expression profiles of hepatocytes, mature adipocyte‐derived dedifferentiated fat (DFAT) cells, hepatic stem cells and adipocytes to identify three transcription factors—Foxa2, Hnf4a and Sall1—that can specifically induce hepatocyte differentiation in DFAT cells.
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影响因子：
46.9
作者：
Azuma, Hisaya;Paulk, Nicole;Grompe, Markus
通讯作者：
Grompe, Markus
化学混合物能够利用单一转录因子对小鼠成纤维细胞进行肝脏重编程
影响因子：
5.9
作者：
Guo R;Tang W;Yuan Q;Hui L;Wang X;Xie X
通讯作者：
Xie X
DOI：
10.1002/ar.b.20079
发表时间：
2005-11-01
期刊：
Anatomical Record Part B:The New Anatomist
影响因子：
--
作者：
Carlson, Bruce M.
通讯作者：
Carlson, Bruce M.
影响因子：
23.9
作者：
Du, Yuanyuan;Wang, Jinlin;Deng, Hongkui
通讯作者：
Deng, Hongkui
影响因子：
14.9
作者：
Barrett T;Troup DB;Wilhite SE;Ledoux P;Rudnev D;Evangelista C;Kim IF;Soboleva A;Tomashevsky M;Marshall KA;Phillippy KH;Sherman PM;Muertter RN;Edgar R
通讯作者：
Edgar R