ArticleThe Journal of biological chemistry2010
Hepatocyte nuclear factor-4alpha induces transdifferentiation of hematopoietic cells into hepatocytes.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Cell-Based Regeneration and Treatment of Liver Diseases.International journal of molecular sciences · 2021Review
- Progress and Challenges in the Use of a Liver-on-a-Chip for Hepatotropic Infectious Diseases.Micromachines · 2021Review
- Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD.Journal of clinical medicine · 2020Article
- Bioluminescence Imaging of Transplanted Mesenchymal Stem Cells by Overexpression of Hepatocyte Nuclear Factor4α: Tracking Biodistribution and Survival.Molecular imaging and biology · 2019Article
- Stem Cell Strategies to Evaluate Idiosyncratic Drug-induced Liver Injury.Journal of clinical and translational hepatology · 2014Review
- Transdifferentiation of human fibroblasts into hepatocyte-like cells by defined transcriptional factors.Hepatology international · 2013Article
- Cell fusion reprogramming leads to a specific hepatic expression pattern during mouse bone marrow derived hepatocyte formation in vivo.PloS one · 2012Article
- Efficient generation of functional hepatocytes from human embryonic stem cells and induced pluripotent stem cells by HNF4α transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-progress and prospects.Advanced drug delivery reviews · 2011Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hematopoietic stem cells can directly transdifferentiate into hepatocytes because of cellular plasticity, but the molecular basis of transdifferentiation is not known. Here, we show the molecular basis using lineage-depleted oncostatin M receptor beta-expressing (Lin(-)OSMRbeta(+)) mouse bone marrow cells in a hepatic differentiation culture system. Differentiation of the cells was marked by the expression of albumin. Hepatocyte nuclear factor (HNF)-4alpha was expressed and translocated into the nuclei of the differentiating cells. Suppression of its activation in OSM-neutralized culture medium inhibited cellular differentiation. Ectopic expression of full-length HNF4alpha in 32D myeloid cells resulted in decreased myeloid colony-forming potential and increased expression of hepatocyte-specific genes and proteins. Nevertheless, the neohepatocytes produced in culture expressed active P450 enzyme. The obligatory role of HNF4alpha in hepatic differentiation was confirmed by transfecting Lin(-)OSMRbeta(+) cells with dominant negative HNF4alpha in the differentiation culture because its expression inhibited the transcription of the albumin and tyrosine aminotransferase genes. The loss and gain of functional activities strongly suggested that HNF4alpha plays a central role in the transdifferentiation process. For the first time, this report demonstrates the mechanism of transdifferentiation of hematopoietic cells into hepatocytes, in which HNF4alpha serves as a molecular switch.
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