Adipogenic Differentiation of hMSCs is Mediated by Recruitment of IGF‐1R Onto the Primary Cilium Associated with Cilia Elongation

This study tested the hypothesis that changes in primary cilia structure are required for stem cell differentiation. hMSCs expressed primary cilia which were labelled with acetylated alpha tubulin and visualized by confocal microscopy. Chemically induced differentiation resulted in lineage specific changes in cilia length and prevalence independent of cell cycle. In particular adipogenic differentiation resulted in cilia elongation associated with the presence of dexamethasone, whilst insulin had an inhibitory effect on cilia length. Over a seven day time course adipogenic differentiation media resulted in cilia elongation within two days followed by increased nuclear PPARγ levels, an early marker of adipogenesis. Cilia elongation was associated with increased trafficking of IGF‐1Rβ into the cilium. This was reversed upon inhibition of elongation by IFT‐88 siRNA transfection which also decreased nuclear PPARγ. This is the first study to show that adipogenic differentiation requires primary cilia elongation associated with the recruitment of IGF‐1Rβ onto the cilium. This study may lead to the development of cilia‐targeted therapies for controlling adipogenic differentiation and associated conditions such as obesity. This article is protected by copyright. All rights reserved.

Source: Stem Cells - February 18, 2015 Category: Stem Cells Authors: Melis T. Dalbay, Stephen D. Thorpe, John T. Connelly, J. Paul Chapple, Martin M. Knight Tags: Tissue‐specific stem cells Source Type: research