Inhibition of Protein Kinase C Signaling Maintains Rat Embryonic Stem Cell Pluripotency |
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Authors: | Ganeshkumar Rajendran Debasree Dutta James Hong Arindam Paul Biswarup Saha Biraj Mahato Soma Ray Pratik Home Avishek Ganguly Mark L Weiss Soumen Paul |
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Institution: | From the ‡Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160 and ;the §Department of Anatomy and Physiology, Kansas State University, College of Veterinary Medicine, Manhattan, Kansas 66506 |
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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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Keywords: | Chromatin Modification Embryonic Stem Cell NF-κ B PKC Rat |
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