Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells

(2016) Forced expression of Hnf1b/Foxa3 promotes hepatic fate of embryonic stem cells. Biochemical and Biophysical Research Communications.

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Embryonic stem (ES) cell-derived hepatocytes have the potential to be used for basic research, regenerative medicine, and drug discovery. Recent reports demonstrated that in addition to conventional differentiation inducers such as chemical compounds and cytokines, overexpression of lineage-specific transcription factors could induce ES cells to differentiate to a hepatic fate. Here, we hypothesized that lentivirus-mediated inducible expression of hepatic lineage transcription factors could enhance mouse ES cells to hepatocyte-like cells. We screened the effects of candidate transcription factors Hnf1b, Hnf1a, Hnf4a, Foxa1, Foxa3 and Hex, and determined that the combination of Hnf1b/Foxa3 promoted expression of several hepatic lineage-specific markers and proteins, in addition to glycogen storage, ICG uptake, and secretion of albumin and urea. The differentiated cells were engraftable and expressed albumin when transplanted into a carbon tetrachloride-injured mouse model. These results demonstrated the crucial role of Hnf1b and Foxa3 in hepatogenesis in vitro and provided a valuable tool for the efficient differentiation of HLCs from ES cells. © 2016 Elsevier Inc. All rights reserved.

Item Type: Article
Keywords: albumin; carbon tetrachloride; hepatocyte nuclear factor 1alpha; hepatocyte nuclear factor 1beta; hepatocyte nuclear factor 3alpha; hepatocyte nuclear factor 3gamma; hepatocyte nuclear factor 4alpha; lentivirus vector; transcription factor; transcription factor Hex; unclassified drug; urea; Foxa3 protein, mouse; hepatocyte nuclear factor 1beta; hepatocyte nuclear factor 3gamma; Hnf1b protein, mouse, animal cell; animal experiment; animal model; Article; cell differentiation; cell fate; cell lineage; controlled study; embryo; engraftment; gene overexpression; human; human cell; liver cell; liver development; mouse; mouse embryonic stem cell; mouse model; nonhuman; priority journal; protein expression; screening; animal; cell culture; cytology; embryonic stem cell; gene expression regulation; metabolism; physiology, Animals; Cell Differentiation; Cells, Cultured; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Hepatocyte Nuclear Factor 1-beta; Hepatocyte Nuclear Factor 3-gamma; Hepatocytes; Mice
Page Range: pp. 199-205
Journal or Publication Title: Biochemical and Biophysical Research Communications
Volume: 474
Number: 1
Publisher: Elsevier B.V.
Identification Number: 10.1016/j.bbrc.2016.04.102
ISSN: 0006291X
Depositing User: مهندس جمال محمودپور

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