Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data of hepatocytes isolated from chimeric mouse livers repopulated with human hepatocytes and from normal human livers

ABSTRACT: We generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed. Additionally, we performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with hepatocytes. A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) were examined. The chimeric mice were generated by transplantation of 2 different donor hepatocytes. Hepatocytes were isolated from the mouse livers and normal human livers, and their cDNAs were used for microarray analysis. Total RNA isolated from human tissues and cell cultures were labeled and hybridized to the GeneChip Human Genome U133 Plus 2.0 Array according to the manufacturer's protocol.

ORGANISM(S): Mus musculus

SUBMITTER: Fuyuki Miya

PROVIDER: E-GEOD-33846 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.

Tateno Chise C Miya Fuyuki F Wake Kenjiro K Kataoka Miho M Ishida Yuji Y Yamasaki Chihiro C Yanagi Ami A Kakuni Masakazu M Wisse Eddie E Verheyen Fons F Inoue Kouji K Sato Kota K Kudo Atsushi A Arii Shigeki S Itamoto Toshiyuki T Asahara Toshimasa T Tsunoda Tatsuhiko T Yoshizato Katsutoshi K

Laboratory investigation; a journal of technical methods and pathology 20121112 1

We previously produced mice with human hepatocyte (h-hep) chimeric livers by transplanting h-heps into albumin enhancer/promoter-driven urokinase-type plasminogen activator-transgenic severe combined immunodeficient (SCID) mice with liver disease. The chimeric livers were constructed with h-heps, mouse hepatocytes, and mouse hepatic sinusoidal cells (m-HSCs). Here, we investigated the morphological features of the chimeric livers and the h-hep gene expression profiles in the xenogeneic animal bo ...[more]

PMID: 23147226

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Project description:It is well-known that isolation and cultivation of primary hepatocytes causes major gene expression alterations. In the present genome-wide, time resolved study of cultivated human and mouse hepatocytes, we made the observation that expression changes in culture strongly resemble alterations in liver diseases. Hepatocytes of both species were cultivated in collagen sandwich and in monolayer conditions. Genome-wide data were also obtained from human NAFLD, cirrhosis, HCC, and hepatitis B virus infected tissue as well as mouse livers after partial hepatectomy, CCl4 intoxication, obesity, HCC and LPS. A strong similarity between cultivation and disease induced expression alterations was observed. For example, expression changes in hepatocytes induced by one day cultivation and one day CCl4 exposure in vivo correlated with R=0.615 (P<0.001). Interspecies comparison identified predominantly similar responses in human and mouse hepatocytes but also a minority of genes that responded differently. Unsupervised clustering of altered genes identified three main clusters: (1) downregulated genes corresponding to mature liver functions, (2) upregulation of an inflammation/RNA-processing cluster, (3) upregulated migration/cell-cycle associated genes. Gene regulatory network analysis highlights overrepresented and deregulated HNF4 and CAR (cluster 1), KrÃ¼ppel-like factors MafF and ELK1 (cluster 2) as well as ETF (cluster 3) among the interspecies conserved key regulators of expression changes. Interventions ameliorating but by far not abrogating cultivation-induced responses include removal of non-parenchymal cells, generation of the hepatocytesâ own matrix in spheroids, supplementation with bile salts and siRNA mediated suppression of key transcription factors. In conclusion, the study shows that gene regulatory network alterations of cultivated hepatocytes resemble those of inflammatory liver diseases and should therefore be considered and exploited as disease models.

Dataset Information

Expression data of hepatocytes isolated from chimeric mouse livers repopulated with human hepatocytes and from normal human livers

Publications

Morphological and microarray analyses of human hepatocytes from xenogeneic host livers.

Similar Datasets

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