Multiphasic and Dynamic Changes in Alternative Splicing during Induction of Pluripotency Are Coordinated by Numerous RNA-Binding Proteins.

Autor:	Cieply B; Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Park JW; Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Computer Engineering and Computer Science, University of Louisville, Louisville, KY 40292, USA; KBRIN Bioinformatics Core, University of Louisville, Louisville, KY 40292, USA., Nakauka-Ddamba A; Department of Biomedical Sciences and Institute for Regenerative Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Bebee TW; Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Guo Y; Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA; School of Computer Science, Northwestern Polytechnical University, Xian 710072, China., Shang X; School of Computer Science, Northwestern Polytechnical University, Xian 710072, China., Lengner CJ; Department of Biomedical Sciences and Institute for Regenerative Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Xing Y; Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA. Electronic address: yxing@ucla.edu., Carstens RP; Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: russcars@upenn.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 Apr 12; Vol. 15 (2), pp. 247-55. Date of Electronic Publication: 2016 Mar 31.
DOI:	10.1016/j.celrep.2016.03.025
Abstrakt:	Alternative splicing (AS) plays a critical role in cell fate transitions, development, and disease. Recent studies have shown that AS also influences pluripotency and somatic cell reprogramming. We profiled transcriptome-wide AS changes that occur during reprogramming of fibroblasts to pluripotency. This analysis revealed distinct phases of AS, including a splicing program that is unique to transgene-independent induced pluripotent stem cells (iPSCs). Changes in the expression of AS factors Zcchc24, Esrp1, Mbnl1/2, and Rbm47 were demonstrated to contribute to phase-specific AS. RNA-binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS during reprogramming by different RNA-binding proteins. Ectopic expression of Esrp1 enhanced reprogramming, in part by modulating the AS of the epithelial specific transcription factor Grhl1. These data represent a comprehensive temporal analysis of the dynamic regulation of AS during the acquisition of pluripotency. (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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