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Comparative transcriptomics of hepatic differentiation of human pluripotent stem cells and adult human liver tissue

Journal article
Authors Nidal Ghosheh
B. Kuppers-Munther
A. Asplund
J. Edsbagge
B. Ulfenborg
T. B. Andersson
P. Bjorquist
C. X. Andersson
Helena Carén
Stina Simonsson
P. Sartipy
J. Synnergren
Published in Physiological Genomics
Volume 49
Issue 8
Pages 430-446
ISSN 1094-8341
Publication year 2017
Published at Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
Sahlgrenska Cancer Center
Institute of Biomedicine, Department of Pathology
Pages 430-446
Language en
Links doi.org/10.1152/physiolgenomics.000...
Keywords human pluripotent stem cell, stem cell-derived hepatocytes, liver tissue, differentiation, HEPATOCYTE-LIKE CELLS, GENE-EXPRESSION, BIOLOGICAL NETWORKS, MODELS, METABOLISM, CHALLENGES, PATHWAY, INJURY, LEVEL, FETAL
Subject categories Cell and Molecular Biology

Abstract

Hepatocytes derived from human pluripotent stem cells (hPSC-HEP) have the potential to replace presently used hepatocyte sources applied in liver disease treatment and models of drug discovery and development. Established hepatocyte differentiation protocols are effective and generate hepatocytes, which recapitulate some key features of their in vivo counterparts. However, generating mature hPSC-HEP remains a challenge. In this study, we applied transcriptomics to investigate the progress of in vitro hepatic differentiation of hPSCs at the developmental stages, definitive endoderm, hepatoblasts, early hPSC-HEP, and mature hPSC-HEP, to identify functional targets that enhance efficient hepatocyte differentiation. Using functional annotation, pathway and protein interaction network analyses, we observed the grouping of differentially expressed genes in specific clusters representing typical developmental stages of hepatic differentiation. In addition, we identified hub proteins and modules that were involved in the cell cycle process at early differentiation stages. We also identified hub proteins that differed in expression levels between hPSC-HEP and the liver tissue controls. Moreover, we identified a module of genes that were expressed at higher levels in the liver tissue samples than in the hPSC-HEP. Considering that hub proteins and modules generally are essential and have important roles in the protein-protein interactions, further investigation of these genes and their regulators may contribute to a better understanding of the differentiation process. This may suggest novel target pathways and molecules for improvement of hPSC-HEP functionality, having the potential to finally bring this technology to a wider use.

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