Repository of Research and Investigative Information

Repository of Research and Investigative Information

Kurdistan University of Medical Sciences

Forced expression of Hnf4a induces hepatic gene activation through directed differentiation

(2016) Forced expression of Hnf4a induces hepatic gene activation through directed differentiation. Biochemical and Biophysical Research Communications.

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Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Embryonic stem (ES) cells are capable of unlimited self-renewal and have a diverse differentiation potential. These unique features make ES cells as an attractive source for developmental biology studies. Having the mature hepatocyte in the lab with functional activities is valuable in drug discovery studies. Overexpression of hepatocyte lineage-specific transcription factors (TFs) becomes a promising approach in pluripotent cell differentiation toward liver cells. Many studies generate transgenic ES cell lines to examine the effects of specific TFs overexpression in cell differentiation. In the present report, we have addressed whether a suspension or adherent model of differentiation is an appropriate way to study the role of Hnf4a overexpression. We generated ES cells that carried a doxycycline (Dox)-inducible Hnf4a using lentiviral vectors. The transduced cells were subjected to induced Hnf4a overexpression through both spontaneous and directed differentiation methods. Gene expression analysis showed substantially increased expression of hepatic gene markers, particularly Ttr and endogenous Hnf4a, in transduced cells differentiated by the directed approach. These results demonstrated that forced expression of TFs during directed differentiation would be an appropriate way to study relevant gene activation and the effects of overexpression in the context of hepatic differentiation. © 2016 Elsevier Inc.

Item Type: Article
Keywords: doxycycline; hepatocyte nuclear factor 4alpha; lentivirus vector; green fluorescent protein; hepatocyte nuclear factor 4; Hnf4a protein, mouse, animal cell; Article; cell differentiation; embryonic stem cell; gene activation; gene expression; marker gene; mouse; nonhuman; priority journal; protein expression; animal; cell culture; cell differentiation; cytology; gene expression regulation; genetics; liver; metabolism; physiology; promoter region; transgenic mouse, Animals; Cell Differentiation; Cells, Cultured; Embryonic Stem Cells; Gene Expression Regulation; Green Fluorescent Proteins; Hepatocyte Nuclear Factor 4; Liver; Mice; Mice, Transgenic; Promoter Regions, Genetic
Page Range: pp. 313-318
Journal or Publication Title: Biochemical and Biophysical Research Communications
Volume: 476
Number: 4
Publisher: Elsevier B.V.
Identification Number: 10.1016/j.bbrc.2016.05.119
ISSN: 0006291X
Depositing User: مهندس جمال محمودپور
URI: http://eprints.muk.ac.ir/id/eprint/522

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