Enhanced Development of Skeletal Myotubes from Porcine Induced Pluripotent Stem Cells

• DOI: 10.1038/srep41833
• Publication Date: 2017-02-06T14:25:57Z
• Authors: Nicholas J. Genovese; Timothy L. Domeier; Bhanu Prakash V. ...; R. Michael Roberts
• Keywords: 0301 basic medicine; 2. Zero hunger; Pyridines; Swine; Induced Pluripotent Stem Cells; Muscle Fibers, Skeletal; Apoptosis; Cell Differentiation; Muscle Development; Article; 03 medical and health sciences; Pyrimidines; Animals; Cell Lineage; Wnt Signaling Pathway; beta Catenin

Abstract The pig is recognized as a valuable model in biomedical research addition to its agricultural importance. Here we describe means for generating skeletal muscle efficiently from porcine induced pluripotent stem cells (piPSC) vitro thereby providing versatile platform applications ranging regenerative biology the ex vivo cultivation of meat. GSK3B inhibitor, CHIR99021 was employed suppress apoptosis, elicit WNT signaling events and drive naïve-type piPSC along mesoderm lineage, and, combination with DNA methylation inhibitor 5-aza-cytidine, activate an early transcription program. Terminal differentiation then by activation ectopically expressed MYOD1 . Myotubes, characterized myofibril development both spontaneous stimuli-elicited excitation-contraction coupling cycles appeared within 11 days. Efficient lineage-specific confirmed uniform NCAM1 myosin heavy chain expression. These results provide approach that potentially applicable other cell lines forms muscle.