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Highly efficient conversion of mouse fibroblasts into functional hepatic cells under chemical induction

Journal of Molecular Cell Biology 2023年第11期15卷 43-57页

作者： Zhi Zhong Jiangchuan Du Xiangjie Zhu lingting guan Yanyu Hu Peilin Zhang Hongyang Wang Fudan University Shanghai Cancer Center Department of OncologyShanghai Medical CollegeFudan UniversityShanghai 200032China National Center for Liver Cancer Naval Medical UniversityShanghai 201805China Institute of Metabolism and Integrative Biology Fudan UniversityShanghai 200438China

Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction ***,these methods have their own deficiencies that restrict the therapeutic applications of such induced *** this study,we present a transgene-free,highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts(MEFs).Using a small molecule cocktail(SMC)as an inducer,MEFs can be directly reprogrammed into hepatocyte-like cells,bypassing the intermediate stages of pluripotent and immature *** chemical-induced hepatocyte-like cells(ciHeps)closely resemble mature primary hepatocytes in terms of morphology,biological behavior,gene expression patterns,marker expression levels,and hepatic ***,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver *** can also ameliorate liver fibrosis caused by chronic injuries and enhance liver ***,ciHeps exhibit no tumorigenic potential either in vitro or in ***,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into *** results indicate that this transgene-free,chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic ***,this method also sheds light on the direct reprogramming of other cell types under chemical induction.

关键词： direct cell reprogramming chemicals fibroblasts hepatocyte-like cells high efficiency regenerative medicine

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