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

Benjamin Cieply; Juw Won Park; Angela Nakauka-Ddamba; Thomas W. Bebee; Yang Guo; Xuequn Shang; Christopher J. Lengner; Yi Xing; Russ P. Carstens

doi:10.1016/j.celrep.2016.03.025

Cell Reports (Apr 2016)

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

Benjamin Cieply,
Juw Won Park,
Angela Nakauka-Ddamba,
Thomas W. Bebee,
Yang Guo,
Xuequn Shang,
Christopher J. Lengner,
Yi Xing,
Russ P. Carstens

Affiliations

Benjamin Cieply: Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Juw Won Park: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA
Angela Nakauka-Ddamba: Department of Biomedical Sciences and Institute for Regenerative Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Thomas W. Bebee: Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Yang Guo: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA
Xuequn Shang: School of Computer Science, Northwestern Polytechnical University, Xian 710072, China
Christopher J. Lengner: Department of Biomedical Sciences and Institute for Regenerative Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Yi Xing: Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095, USA
Russ P. Carstens: Department of Medicine and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

DOI: https://doi.org/10.1016/j.celrep.2016.03.025
Journal volume & issue: Vol. 15, no. 2
pp. 247 – 255

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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