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Homo sapiens

ABSTRACT: Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [shRNA]

OTHER RELATED OMICS DATASETS IN: GSE69351GSE62777

PROVIDER: PRJNA290154 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2106044_1.fastq.gz	Fastqsanger.gz
	SRR2106044_2.fastq.gz	Fastqsanger.gz
	SRR2106045_1.fastq.gz	Fastqsanger.gz
	SRR2106045_2.fastq.gz	Fastqsanger.gz
	SRR2106046_1.fastq.gz	Fastqsanger.gz

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Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

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Defining a molecular roadmap of cellular reprogramming into iPS Cells [DNA methylation]

Project description:Factor-induced reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is inefficient, complicating mechanistic studies. Here, we examined defined intermediate cell populations poised to becoming iPSCs by genome-wide analyses. We show that induced pluripotency elicits two transcriptional waves, which are driven by c-Myc/Klf4 (first wave) and Oct4/Sox2/Klf4 (second wave). Cells that become refractory to reprogramming activate the first but fail to initiate the second transcriptional wave and can be rescued by elevated expression of all four factors. The establishment of bivalent domains occurs gradually after the first wave, whereas changes in DNA methylation take place after the second wave when cells acquire stable pluripotency. This integrative analysis allowed us to identify genes that act as roadblocks during reprogramming and surface markers that further enrich for cells prone to forming iPSCs. Collectively, our data offer new mechanistic insights into the nature and sequence of molecular events inherent to cellular reprogramming. DNA methylation profiles obtained at different timepoints during reprogramming of somatic cells: Day 0, +3, +6, +9 and iPSC

2013-03-18 | E-GEOD-45248 | biostudies-arrayexpress

Defining a molecular roadmap of cellular reprogramming into iPS Cells [DNA methylation]

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Macro histone variants preserve cell identity by preventing the gain of H3K4me2 during reprogramming

Project description:Transcription factor-induced reprogramming of somatic cells to pluripotency is a very inefficient process, probably due to the existence of important epigenetic barriers that are imposed during differentiation and that contribute to preserve cell identity. In an effort to decipher the molecular nature of these barriers, we followed a genome-wide approach, in which we identified macro histone variants (macroH2A) as highly expressed in human somatic cells but downregulated after reprogramming to pluripotency, as well as strongly induced during differentiation. Knock down of macro histone variants in human keratinocytes increased the efficiency of reprogramming to pluripotency, while overexpression had opposite effects. Genome-wide occupancy profiles show that in human keratinocytes macroH2A.1 preferentially occupies genes that are expressed at low levels and are marked with H3K27me3, including pluripotency-related genes and bivalent developmental regulators, at which its presence prevents the regain of H3K4me2 during reprogramming, over imposing an additional layer of repression that preserves cell identity. Gemone wide occupancy of HA:macroH2A.1 in human keratinocytes

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