RARβ2-dependent signaling represses neuronal differentiation in mouse ES cells.

Autor: Kona SL; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA., Shrestha A; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA., Yi X; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA., Joseph S; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA., Barona HM; Department of Physics and Mathematics, Southern University and A&M College, Baton Rouge, LA 70813, USA., Martinez-Ceballos E; Department of Biological Sciences and Chemistry, Southern University and A&M College, Baton Rouge, LA 70813, USA. Electronic address: Eduardo_martinez@subr.edu.
Jazyk: angličtina
Zdroj: Differentiation; research in biological diversity [Differentiation] 2017 Nov - Dec; Vol. 98, pp. 55-61. Date of Electronic Publication: 2017 Nov 10.
DOI: 10.1016/j.diff.2017.11.002
Abstrakt: Embryonic Stem (ES) cells are pluripotent cells that can be induced to differentiate into cells of all three lineages: mesoderm, endoderm, and ectoderm. In culture, ES cells can be differentiated into mature neurons by treatment with Retinoic Acid (RA) and this effect is mediated mainly through the activation of the RA nuclear receptors (RAR α, β, and γ), and their isoforms. However, little is known about the role played by specific RAR types on ES cell differentiation. Here, we found that treatment of ES cells with AC55649, an RARβ2 agonist, increased endodermal marker gene expression. On the other hand, we found that the inhibition of RARβ with 5μM LE135, together with RA treatment, increased the efficiency of mouse ES cell differentiation into neurons by more than 4-fold as compared to cells treated with RA only. Finally, we performed proteomic analyses on ES cells treated with RA vs RA plus AC55649 in order to identify the signaling pathways activated by the RARβ agonist. Our proteomic analyses using antibody microarrays indicated that proteins such as p38 and AKT were upregulated in cells treated with RA plus the agonist, as compared to cells treated with RA alone. Our results indicate that RARβ may function as a repressor of neuronal differentiation through the activation of major cell signaling pathways, and that the pharmacological inhibition of this nuclear receptor may constitute a novel method to increase the efficiency of ES to neuronal differentiation in culture.
(Copyright © 2017 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: