title: Inhibition of protein kinase C signaling maintains rat embryonic stem cell pluripotency.
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.
authors.affiliation: Institute for Reproductive Health and Regenerative Medicine, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
authors.forename: Ganeshkumar
authors.initials: G
authors.lastname: Rajendran
authors.forename: Debasree
authors.initials: D
authors.lastname: Dutta
authors.forename: James
authors.initials: J
authors.lastname: Hong
authors.forename: Arindam
authors.initials: A
authors.lastname: Paul
authors.forename: Biswarup
authors.initials: B
authors.lastname: Saha
authors.forename: Biraj
authors.initials: B
authors.lastname: Mahato
authors.forename: Soma
authors.initials: S
authors.lastname: Ray
authors.forename: Pratik
authors.initials: P
authors.lastname: Home
authors.forename: Avishek
authors.initials: A
authors.lastname: Ganguly
authors.forename: Mark L
authors.initials: ML
authors.lastname: Weiss
authors.forename: Soumen
authors.initials: S
authors.lastname: Paul
mesh_terms: D000818:Animals; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D035683:MicroRNAs / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000201:enzymology*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: C465664:2-(1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl)-3-(1H-indol-3-yl)maleimide; D007211:Indoles; C526366:MIRN29 microRNA, rat; D008301:Maleimides; D035683:MicroRNAs; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; C546082:mirn21 microRNA, rat; C497257:Prkce protein, rat; D051744:Protein Kinase C-epsilon
keywords: Chromatin Modification; Embryonic Stem Cell; NF-κB; PKC; Rat