Angbohang, A;
Wu, N;
Charalambous, T;
Eastlake, K;
Lei, Y;
Kim, YS;
Sun, XH;
(2016)
Downregulation of the Canonical WNT Signaling Pathway by TGF beta 1 Inhibits Photoreceptor Differentiation of Adult Human Muller Glia with Stem Cell Characteristics.
Stem Cells and Development
, 25
(1)
pp. 1-12.
10.1089/scd.2015.0262.
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Abstract
Muller glia are responsible for the retina regeneration observed in zebrafish. Although the human retina harbors Muller glia with stem cell characteristics, there is no evidence that they regenerate the retina after disease or injury. Transforming growth factor-b (TGFb) and Wnt signaling regulate retinal neurogenesis and inflammation, but their roles in the neural differentiation of human Mu¨ller stem cells (hMSC) are not known. We examined hMSC lines in vitro for the expression of various Wnt signaling components and for their modulation by TGFb1, as well as the effect of this cytokine on the photoreceptor differentiation of these cells. Culture of hMSC with a combination of factors that induce photoreceptor differentiation of hMSC (FGF2, taurine, retinoic acid, and insulin-like growth factor type1; FTRI), markedly upregulated the expression of components of the canonical Wnt signaling pathway, including WNT2B, DKK1, and active b-CATENIN. Although FTRI did not modify mRNA expression of WNT5B, a component of the noncanonical/planar cell polarity Wnt pathway, it upregulated its secretion. Furthermore, TGFb1 not only decreased WNT2B expression, but also inhibited FTRI-induced photoreceptor differentiation of hMSC, as determined by expression of the photoreceptor markers NR2E3, RHODOPSIN, and RECOVERIN. Inhibition of TGFb1 signaling by an ALK5 inhibitor prevented TGFb1-induced changes in the expression of the two Wnt ligands examined. More importantly, inhibition of the canonical WNT signaling by XAV-939 prevented FTRI-induced photoreceptor differentiation. These observations suggest that TGFb may play a key role in preventing neural differentiation of hMSC and may constitute a potential target for induction of endogenous regeneration of the human retina.
| Type: | Article |
|---|---|
| Title: | Downregulation of the Canonical WNT Signaling Pathway by TGF beta 1 Inhibits Photoreceptor Differentiation of Adult Human Muller Glia with Stem Cell Characteristics |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1089/scd.2015.0262 |
| Publisher version: | http://dx.doi.org/10.1089/scd.2015.0262 |
| Language: | English |
| Additional information: | Copyright © Angshumonik Angbohang, et al., 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1478606 |
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