Generation of metabolically functional hepatocyte‐like cells from dedifferentiated fat cells by Foxa2, Hnf4a and Sall1 transduction

Autor: Takashi Matsumaru, Shiho Ibayashi, Yoshinao Oki, Reiko Hagiwara, Koichiro Kano
Rok vydání: 2020
Předmět:
Zdroj: Genes to Cells
ISSN: 1365-2443
1356-9597
DOI: 10.1111/gtc.12814
Popis: 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.
Databáze: OpenAIRE
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