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Series GSE3126 Query DataSets for GSE3126
Status Public on Dec 31, 2005
Title Comparison of HNF4 null mouse embryonic livers with control mouse embryonic livers
Organism Mus musculus
Experiment type Expression profiling by array
Summary To study the role of hepatic nuclear factor alpha (HNF4a in hepatogenesis, we used loxP-Cre technology to eliminate it from developing mouse livers.
A comparison of control and experimental livers revealed that hepatocytes lacking HNF4a_failed to fully differentiate. Specifically, HNF4a null liver cells failed to express genes that are markers of mature hepatocytes including Gys2, Pck1, and G6pc. These cells also failed to form normal cellular junctions, which are critical for establishment of the hepatic epithelium [Parviz et al. (2003) Nat.Genet. 34, 292-96]. Because HNF4a functions as a transcription factor, we hypothesized that it regulates liver development by controlling the expression of genes whose products are essential in executing cellular differentiation and morphogenesis. To identify these genes, we compared expression profiles between HNF4a null and wild type E18.5 fetal livers using Affymetrix gene arrays. We identified 564 genes whose expression was decreased by at least 2.5-fold and 34 genes whose expression was increased by at least 2.5-fold when HNF4a was eliminated from hepatocytes. These represent genes involved in diverse molecular pathways, reflecting the pleiotropic phenotype of HNF4a null livers. Our goal was to use the information from the gene arrays to define the mechanisms through which HNF4a controls the generation of the hepatic epithelium. We identified 27 genes from our list of downregulated genes with either defined or predicted roles in cellular junctions and/or adhesion. Most striking was that loss of HNF4a altered the expression of genes encoding proteins involved in virtually all types of cellular junctions including tight junctions (Cldn1, Cldn-2, Cldn-12, Ocln, F11r/Jam1, Cxadr, Crb3), adherens junctions (Cdh1), desmosomes (Dsc2, Pkp2, Krt2-8), and gap junctions (Gjb1, Gjb2). Using immunoblotting and immunohistochemistry, we found that the expression of proteins representing each of these junction types was reduced or absent. Analysis of these genes for the presence of putative HNF4a binding sites revealed that 25 of 27 contain such sites. We have used chromatin immunoprecipitation to confirm that HNF4a occupies several of these sites in vivo, including Cdh1, Cldn1, and F11r/Jam1. From these data, we conclude that HNF4a is a central mediator of the fully differentiated hepatocyte gene expression program and that it orchestrates the expression of cell junction and adhesion proteins required for establishing the hepatic epithelium.
Keywords: E18.5 fetal hnf4 null and control mouse livers
 
Overall design comparison of three hnf4 null livers to three control
 
Citation(s) 16714383
Submission date Aug 13, 2005
Last update date Feb 11, 2019
Contact name Stephen A Duncan
E-mail(s) duncanst@musc.edu
Phone 843-792-9104
Organization name Medical University South Carolina
Department Regenerative Medicine and Cell Biology
Lab Duncan Lab
Street address 173 Ashley Avenue, BSB 6th Floor, Room 657A
City Charleston
State/province SC
ZIP/Postal code 29425
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM69792 HNF4 Control_8
GSM69793 HNF4 Control_1192
GSM69794 HNF4 Control_1193
Relations
BioProject PRJNA93021

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE3126_RAW.tar 36.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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