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

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

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Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficiencies that restrict the therapeutic applica-tions of such induced hepatocytes.In this study,we present a transgene-free,highly efficient chemical-induced direct reprogram-ming 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 hepatoblasts.These 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 functions.Furthermore,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver damage.ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function.Notably,ciHeps exhibit no tumorigenic potential either in vitro or in vivo.Mechanistically,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps.These 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 purposes.Additionally,this method also sheds light on the direct reprogramming of other cell types under chemical induction.

direct cell reprogrammingchemicalsfibroblastshepatocyte-like cellshigh efficiencyregenerative medicine

Zhi Zhong、Jiangchuan Du、Xiangjie Zhu、Lingting Guan、Yanyu Hu、Peilin Zhang、Hongyang Wang

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Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China

National Center for Liver Cancer,Naval Medical University,Shanghai 201805,China

Institute of Metabolism and Integrative Biology,Fudan University,Shanghai 200438,China

National Natural Science Foundation of ChinaNatural Science Foundation of ShanghaiMajor National science and Technology Projects

8147277214ZR14089002018ZX10302207

2023

10.1093/jmcb/mjad071

分子细胞生物学报(英文版)
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

分子细胞生物学报(英文版)

CSTPCDCSCD
影响因子：0.595
ISSN：1673-520X
年,卷(期)：2023.(11)
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