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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE106838 | GEO | 2018/07/27

REPOSITORIES: GEO

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [WGBS]

Project description:Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is extremely inefficient, complicating mechanistic studies. Here, we identified and molecularly characterized rare, early intermediates poised to reprogram with up to 100% efficiency, without perturbing additional genes or pathways. Analysis of these cells uncovered transcription factors (e.g., Tfap2c, Bex2), which are critical for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed a previously unappreciated early wave of DNA demethylation, which is uncoupled from de novo methylation of somatic regions late in reprogramming. Overall, our study underscores the importance of investigating the rare intermediates poised to produce iPSCs, provides novel insights into the mechanisms of reprogramming, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [ATAC-seq]

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 2]

2018-07-27 | GSE106836 | GEO

Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 1]

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Prospective Isolation of Poised iPSC Intermediates Reveals Principles of Cellular Reprogramming.

Project description:Cellular reprogramming converts differentiated cells into induced pluripotent stem cells (iPSCs). However, this process is typically very inefficient, complicating mechanistic studies. We identified and molecularly characterized rare, early intermediates poised to reprogram with up to 95% efficiency, without perturbing additional genes or pathways, during iPSC generation from mouse embryonic fibroblasts. Analysis of these cells uncovered transcription factors (e.g., Tfap2c and Bex2) that are important for reprogramming but dispensable for pluripotency maintenance. Additionally, we observed striking patterns of chromatin hyperaccessibility at pluripotency loci, which preceded gene expression in poised intermediates. Finally, inspection of these hyperaccessible regions revealed an early wave of DNA demethylation that is uncoupled from de novo methylation of somatic regions late in reprogramming. Our study underscores the importance of investigating rare intermediates poised to produce iPSCs, provides insights into reprogramming mechanisms, and offers a valuable resource for the dissection of transcriptional and epigenetic dynamics intrinsic to cell fate change.

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs

Project description:Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [WGBS]

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 2]

Project description:Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 2]

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Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 1]

Project description:Novel Principles of Cellular Reprogramming Revealed by Prospective Isolation and Characterization of Rare Intermediates Poised to Generate iPSCs [RNA-seq 1]

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