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Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins

ABSTRACT: Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins

PROVIDER: PRJNA306681 | ENA |

REPOSITORIES: ENA

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

Project description: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.

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Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins [iPS]

Project description: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 during reprogramming, including a splicing program that is unique to transgene-independent iPS cells. Changes in the expression of alternative splicing factors Zcchc24, Esrp1, Mbnl1/2 and Rbm47 were demonstrated to be key contributors 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. Mouse embryo fibroblasts were isolated from an E12.5 embryo that was homozygous for a TET-OP-OKSM polycistronic transgene targeted to the collagen 1A locus and homozygous for rtTA targeted to the Rosa26 locus. Therefore the expression of the â??4 factors/Yamanaka factorsâ?? that induce pluripotency can be induced with doxycycline treatment. Using this model we isolated RNA in triplicate over a timecourse of 0, 4, 7, 10, 15, 20, days of dox treatment as well as 3 transgene independent clones. Ssea1 MACS purification (Miltenyi Biotec) was used at each time point except zero.

2016-03-15 | E-GEOD-70022 | biostudies-arrayexpress

Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins [iPS]

2016-03-15 | GSE70022 | GEO

Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins [ESRP DKO]

2016-03-15 | GSE76222 | GEO

Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins [ESRP DKO]

Project description: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 during reprogramming, including a splicing program that is unique to transgene-independent iPS cells. Changes in the expression of alternative splicing factors Zcchc24, Esrp1, Mbnl1/2 and Rbm47 were demonstrated to be key contributors 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. ES cells from 3 independent E3.5 blastocysts from either Control (Esrp1 WT/WT; Esrp2 -/-) or Esrp DKO (Esrp1 floxed/floxed; Esrp2 -/-) were transfected with pLVX-EGFP-Cre, puro selected and RNA was isolated 6 days later.

2016-03-15 | E-GEOD-76222 | biostudies-arrayexpress

Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-03-15 | GSE76233 | GEO

Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-03-15 | E-GEOD-76233 | biostudies-arrayexpress

Mus musculus

Project description:Multiphasic and dynamic changes in alternative splicing during induction of pluripotency are coordinated by numerous RNA binding proteins [iPS]

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Induction of Pluripotency by Alternative Factors (RNA-Seq)

Project description:Reprogramming somatic cells to pluripotency represents a paradigm for cell fate determination. A binary logic of closing and opening chromatin provides a simple way to understand iPSC reprogramming driven by both Yamanaka factors or chemicals. Here we apply this logic to the design a seven factor combination, Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F), that reprogram MEFs to chimera competent iPSCs efficiently. RNA- and ATAC-seq reveal differences between 7F and Yamanaka induced pluripotency, 7IP and YIP, in transcriptomic and chromatin accessibility dynamics(CAD). Sall4 emerges as a dominant force that can close and open chromatin with the help of Jdp2 and Glis1 in resetting somatic chromatin to a pluripotent state. These results reveal a previously unknown path between somatic and pluripotent states, open a door for cell fate control.

2019-06-18 | GSE127927 | GEO

Induction of Pluripotency by Alternative Factors (ATAC-Seq)

2019-06-18 | GSE127926 | GEO