[PDF][PDF] Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA-binding proteins
B Cieply, JW Park, A Nakauka-Ddamba, TW Bebee… - Cell reports, 2016 - cell.com
Cell reports, 2016•cell.com
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 …
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 …
Summary
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.
cell.com