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Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor

Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of...

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Autores principales: Guo, Ren, Tang, Wei, Yuan, Qianting, Hui, Lijian, Wang, Xin, Xie, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550014/
https://www.ncbi.nlm.nih.gov/pubmed/28757167
http://dx.doi.org/10.1016/j.stemcr.2017.06.013
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author Guo, Ren
Tang, Wei
Yuan, Qianting
Hui, Lijian
Wang, Xin
Xie, Xin
author_facet Guo, Ren
Tang, Wei
Yuan, Qianting
Hui, Lijian
Wang, Xin
Xie, Xin
author_sort Guo, Ren
collection PubMed
description Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah(−)/(−)) mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps.
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spelling pubmed-55500142017-08-17 Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor Guo, Ren Tang, Wei Yuan, Qianting Hui, Lijian Wang, Xin Xie, Xin Stem Cell Reports Article Liver or hepatocytes transplantation is limited by the availability of donor organs. Functional hepatocytes independent of the donor sources may have wide applications in regenerative medicine and the drug industry. Recent studies have demonstrated that chemical cocktails may induce reprogramming of fibroblasts into a range of functional somatic cells. Here, we show that mouse fibroblasts can be transdifferentiated into the hepatocyte-like cells (iHeps) using only one transcription factor (TF) (Foxa1, Foxa2, or Foxa3) plus a chemical cocktail. These iHeps show typical epithelial morphology, express multiple hepatocyte-specific genes, and acquire hepatocyte functions. Genetic lineage tracing confirms the fibroblast origin of these iHeps. More interestingly, these iHeps are expandable in vitro and can reconstitute the damaged hepatic tissues of the fumarylacetoacetate hydrolase-deficient (Fah(−)/(−)) mice. Our study provides a strategy to generate functional hepatocyte-like cells by using a single TF plus a chemical cocktail and is one step closer to generate the full-chemical iHeps. Elsevier 2017-07-27 /pmc/articles/PMC5550014/ /pubmed/28757167 http://dx.doi.org/10.1016/j.stemcr.2017.06.013 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Guo, Ren
Tang, Wei
Yuan, Qianting
Hui, Lijian
Wang, Xin
Xie, Xin
Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title_full Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title_fullStr Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title_full_unstemmed Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title_short Chemical Cocktails Enable Hepatic Reprogramming of Mouse Fibroblasts with a Single Transcription Factor
title_sort chemical cocktails enable hepatic reprogramming of mouse fibroblasts with a single transcription factor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5550014/
https://www.ncbi.nlm.nih.gov/pubmed/28757167
http://dx.doi.org/10.1016/j.stemcr.2017.06.013
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