Inhibition of Protein Kinase C Signaling Maintains Rat Embryonic Stem Cell Pluripotency

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2013 Jul 13

PMID 23846691

Citations 26

Authors

Ganeshkumar Rajendran

Debasree Dutta

James Hong

Arindam Paul

Biswarup Saha

Biraj Mahato

Soma Ray

Pratik Home

Avishek Ganguly

Mark L Weiss

Soumen Paul

Affiliations

Soon will be listed here.

Abstract

Embryonic stem cell (ESC) pluripotency is orchestrated by distinct signaling pathways that are often targeted to maintain ESC self-renewal or their differentiation to other lineages. We showed earlier that inhibition of PKC signaling maintains pluripotency in mouse ESCs. Therefore, in this study, we investigated the importance of protein kinase C signaling in the context of rat ESC (rESC) pluripotency. Here we show that inhibition of PKC signaling is an efficient strategy to establish and maintain pluripotent rESCs and to facilitate reprogramming of rat embryonic fibroblasts to rat induced pluripotent stem cells. The complete developmental potential of rESCs was confirmed with viable chimeras and germ line transmission. Our molecular analyses indicated that inhibition of a PKCζ-NF-κB-microRNA-21/microRNA-29 regulatory axis contributes to the maintenance of rESC self-renewal. In addition, PKC inhibition maintains ESC-specific epigenetic modifications at the chromatin domains of pluripotency genes and, thereby, maintains their expression. Our results indicate a conserved function of PKC signaling in balancing self-renewal versus differentiation of both mouse and rat ESCs and indicate that targeting PKC signaling might be an efficient strategy to establish ESCs from other mammalian species.

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