Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2015; 7(1): 1-10
Published online Jan 26, 2015. doi: 10.4252/wjsc.v7.i1.1
Alternative splicing: An important mechanism in stem cell biology
Kenian Chen, Xiaojing Dai, Jiaqian Wu
Kenian Chen, Xiaojing Dai, Jiaqian Wu, The Vivian L Smith Department of Neurosurgery, The Center for Stem Cell and Regenerative Medicine, University of Texas Medical School at Houston, Houston, TX 77030, United States
Author contributions: Chen K, Dai X and Wu J contributed to this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jiaqian Wu, PhD, The Vivian L Smith Department of Neurosurgery, The Center for Stem Cell and Regenerative Medicine, University of Texas Medical School at Houston, 6431 Fannin St, Houston, TX 77030, United States. jiaqian.wu@uth.tmc.edu
Telephone: +1-713-5003421 Fax: +1-713-5002424
Received: July 23, 2014
Peer-review started: July 24, 2014
First decision: August 28, 2014
Revised: September 3, 2014
Accepted: September 17, 2014
Article in press: December 16, 2014
Published online: January 26, 2015
Abstract

Alternative splicing (AS) is an essential mechanism in post-transcriptional regulation and leads to protein diversity. It has been shown that AS is prevalent in metazoan genomes, and the splicing pattern is dynamically regulated in different tissues and cell types, including embryonic stem cells. These observations suggest that AS may play critical roles in stem cell biology. Since embryonic stem cells and induced pluripotent stem cells have the ability to give rise to all types of cells and tissues, they hold the promise of future cell-based therapy. Many efforts have been devoted to understanding the mechanisms underlying stem cell self-renewal and differentiation. However, most of the studies focused on the expression of a core set of transcription factors and regulatory RNAs. The role of AS in stem cell differentiation was not clear. Recent advances in high-throughput technologies have allowed the profiling of dynamic splicing patterns and cis-motifs that are responsible for AS at a genome-wide scale, and provided novel insights in a number of studies. In this review, we discuss some recent findings involving AS and stem cells. An emerging picture from these findings is that AS is integrated in the transcriptional and post-transcriptional networks and together they control pluripotency maintenance and differentiation of stem cells.

Keywords: Alternative splicing, Stem cell, Pluripotency, Differentiation, Splicing factor

Core tip: Alternative splicing (AS) produces multiple transcript isoforms from a single gene, and the regulation of cell-type-specific splicing pattern is crucial for the properties and functions of cells, including pluripotent stem cells. A better understanding of the role of AS in stem cell pluripotency maintenance and differentiation will offer potential new approaches for enhancing the production of induced pluripotent stem cells and/or better control of cell differentiation for research or therapeutic purposes. In this brief review, we provide a timely update of recent studies related to stem cell regulation and splicing in a genome-wide scale.