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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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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. |
format | Online Article Text |
id | pubmed-5550014 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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