Alternative splicing switching in stem cell lineages

Abstract

The application of stem cells to regenerative medicine depends on a thorough understanding of the molecular mechanisms underlying their pluripotency. Many studies have identified key transcription factor-regulated transcriptional networks and chromatin landscapes of embryonic and a number of adult stem cells. In addition, recent publications have revealed another interesting molecular feature of stem cells— a distinct alternative splicing pattern. Thus, it is possible that both the identity and activity of stem cells are maintained by stem cell-specific mRNA isoforms, while switching to different isoforms ensures proper differentiation. In this review, we will discuss the generality of mRNA isoform switching and its interaction with other molecular mechanisms to regulate stem cell pluripotency, as well as the reprogramming process in which differentiated cells are induced to become pluripotent stem cell-like cells (iPSCs).

Key words： alternative splicing; embryonic stem cells; adult stem cells; stem cell maintenance and differentiation; post-transcriptional regulation; epigenetic regulation

Acknowledgments

We apologize to people whose work cannot be discussed in this review due to space limitation. We thank Dr. Keji Zhao and Chen laboratory members for their critical comments on this review. The work in the Chen laboratory has been supported by Research Grant No. 05-FY09-88 from the March of Dimes Foundation, the R00HD055052 NIH Pathway to Independence Award, R21 HD065089 and R01HD065816 from NICHD, the 49th Mallinckrodt Scholar Award from the Edward Mallinckrodt, Jr. Foundation, the American Federation of Aging Research, the Lucile Packard Foundation, and the Johns Hopkins University start-up funding. And I.C. is supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, USA.

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