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

Journal article

Waraky, A, Aleem, E and Larsson, O (2016). Downregulation of IGF-1 receptor occurs after hepatic linage commitment during hepatocyte differentiation from human embryonic stem cells. Biochemical and Biophysical Research Communications. 478 (4), pp. 1575-1581. https://doi.org/10.1016/j.bbrc.2016.08.157
AuthorsWaraky, A, Aleem, E and Larsson, O
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.

Year2016
JournalBiochemical and Biophysical Research Communications
Journal citation478 (4), pp. 1575-1581
PublisherElsevier
ISSN0006-291X
Digital Object Identifier (DOI)https://doi.org/10.1016/j.bbrc.2016.08.157
Publication dates
Print31 Aug 2016
Publication process dates
Deposited12 Dec 2018
Accepted27 Aug 2016
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Open
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