Document Detail


Direct conversion of mouse fibroblasts to hepatocyte-like cells by defined factors.
MedLine Citation:
PMID:  21716291     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The location and timing of cellular differentiation must be stringently controlled for proper organ formation. Normally, hepatocytes differentiate from hepatic progenitor cells to form the liver during development. However, previous studies have shown that the hepatic program can also be activated in non-hepatic lineage cells after exposure to particular stimuli or fusion with hepatocytes. These unexpected findings suggest that factors critical to hepatocyte differentiation exist and become activated to induce hepatocyte-specific properties in different cell types. Here, by screening the effects of twelve candidate factors, we identify three specific combinations of two transcription factors, comprising Hnf4α plus Foxa1, Foxa2 or Foxa3, that can convert mouse embryonic and adult fibroblasts into cells that closely resemble hepatocytes in vitro. The induced hepatocyte-like (iHep) cells have multiple hepatocyte-specific features and reconstitute damaged hepatic tissues after transplantation. The generation of iHep cells may provide insights into the molecular nature of hepatocyte differentiation and potential therapies for liver diseases.
Authors:
Sayaka Sekiya; Atsushi Suzuki
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-29
Journal Detail:
Title:  Nature     Volume:  475     ISSN:  1476-4687     ISO Abbreviation:  Nature     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-21     Completed Date:  2011-08-30     Revised Date:  2012-01-31    
Medline Journal Info:
Nlm Unique ID:  0410462     Medline TA:  Nature     Country:  England    
Other Details:
Languages:  eng     Pagination:  390-3     Citation Subset:  IM    
Affiliation:
Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE29725
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Differentiation* / genetics
Cells, Cultured
Embryo, Mammalian / cytology
Fibroblasts / cytology*
Hepatocyte Nuclear Factor 3-alpha / genetics,  metabolism
Hepatocyte Nuclear Factor 3-beta / genetics,  metabolism
Hepatocyte Nuclear Factor 3-gamma / genetics,  metabolism
Hepatocyte Nuclear Factor 4 / genetics,  metabolism
Hepatocytes / cytology*,  metabolism,  transplantation
Hydrolases / deficiency
Liver / cytology,  enzymology,  physiology
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Chemical
Reg. No./Substance:
0/Foxa1 protein, mouse; 0/Foxa2 protein, mouse; 0/Foxa3 protein, mouse; 0/Hepatocyte Nuclear Factor 3-alpha; 0/Hepatocyte Nuclear Factor 4; 0/Hnf4a protein, mouse; 135845-91-9/Hepatocyte Nuclear Factor 3-gamma; 135845-92-0/Hepatocyte Nuclear Factor 3-beta; EC 3.-/Hydrolases; EC 3.7.1.2/fumarylacetoacetase
Comments/Corrections
Comment In:
Nat Rev Gastroenterol Hepatol. 2011 Sep;8(9):474   [PMID:  21892130 ]
Hepatology. 2012 Jan;55(1):316-8   [PMID:  22190377 ]
Cell Stem Cell. 2011 Aug 5;9(2):89-91   [PMID:  21816357 ]

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