title: Downregulation of IGF-1 receptor occurs after hepatic linage commitment during hepatocyte differentiation from human embryonic stem cells.
abstract: The insulin-like growth factor 1 receptor (IGF-1R) has been suggested to be involved in hepatocyte differentiation. Human hepatocyte cancer cells and stem cells are known to express IGF-1R whereas normal hepatocytes do not. In the present study we optimized a differentiation protocol and verified the different stages by established markers. The expression levels of IGF-1R and major downstream signaling proteins during differentiation from human embryonic stem cells (hESC) to mature hepatocytes were investigated. We could only demonstrate a minor decrease in IGF-1R expression during endodermal differentiation compared to hESC, but declined substantially (>50%) after hepatic lineage commitment during the hepatocyte specification and maturation stages. This downregulation was paralleled by an upregulation of ERK 1/2, AKT and insulin substrate-1. Neither inhibition nor activation of IGF-1R had any essential effect on endoderm differentiation of human embryonic stem cells. Therefore, our data suggest that IGF-1R downregulation may have a regulatory impact after initiation of hepatic lineage commitment.
authors: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden. Electronic address: ahmed.waraky@ki.se.
authors: Ahmed
authors: A
authors: Waraky
authors: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden; Institute of Molecular Medicine at Phoenix Children's Hospital, Phoenix, AZ, USA; University of Arizona College of Medicine-Phoenix, Department of Child Health, Phoenix, AZ, USA; Alexandria University, Faculty of Science, Department of Zoology, Alexandria, Egypt.
authors: Eiman
authors: E
authors: Aleem
authors: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
authors: Olle
authors: O
authors: Larsson
mesh_terms: D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D015536:Down-Regulation; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
chemical_list: D017526:Receptor, IGF Type 1
keywords: Differentiation; Hepatocyte; IGF-1R