TY - JOUR
T1 - Multiphasic and Dynamic Changes in Alternative Splicing during Induction of Pluripotency Are Coordinated by Numerous RNA-Binding Proteins
AU - Cieply, Benjamin
AU - Park, Juw Won
AU - Nakauka-Ddamba, Angela
AU - Bebee, Thomas W.
AU - Guo, Yang
AU - Shang, Xuequn
AU - Lengner, Christopher J.
AU - Xing, Yi
AU - Carstens, Russ P.
N1 - Publisher Copyright:
© 2016 The Authors.
PY - 2016/4/12
Y1 - 2016/4/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962045599&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2016.03.025
DO - 10.1016/j.celrep.2016.03.025
M3 - 文章
C2 - 27050523
AN - SCOPUS:84962045599
SN - 2211-1247
VL - 15
SP - 247
EP - 255
JO - Cell Reports
JF - Cell Reports
IS - 2
ER -