Downregulation of IGF-1 receptor occurs after hepatic linage commitment during hepatocyte differentiation from human embryonic stem cells

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• 作者：Ahmed Waraky^a ; ^{ahmed.waraky@ki.se" class="auth_mail" title="E-mail the corresponding author} ; Eiman Aleem^a ; ^b ; ^c ; ^d ; Olle Larsson^a
• 关键词：IGF-1R ; Hepatocyte ; Differentiation
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2016
• 出版时间：30 September 2016
• 年：2016
• 卷：478
• 期：4
• 页码：1575-1581
• 全文大小：1445 K

文摘

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.