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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

ABSTRACT: BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

PROVIDER: PRJNA611573 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11272883_1.fastq.gz	Fastqsanger.gz
	SRR11272883_2.fastq.gz	Fastqsanger.gz
	SRR11272884_1.fastq.gz	Fastqsanger.gz
	SRR11272884_2.fastq.gz	Fastqsanger.gz
	SRR11272885_1.fastq.gz	Fastqsanger.gz

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

Project description:BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [RNA-Seq]

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [RNA-Seq]

Project description:Mouse naive and primed pluripotent stem cells, ESC and EpiSC, represent two distinct stages of pluripotency. Here we report that BMP4 drives primed to naive transition or PNT by reprogramming chromatin accessibility. ATAC-seq reveals that a short pulse of BMP4 triggers EpiSCs to close 26409 and open 6428 loci to reach an intermediate state that continue to open 18744 and close 7042 loci under 2iL until reaching a naive state, following with a dramatic reactivation of the silenced X chromosome. Among loci opened by BMP4 are those encoding Id1, Tfap2c/2a and Zbtb7b that synergistically drive PNT without BMP4. Tfap2c-/- ESCs or EpiSCs self-renew normally, while the former capable of differentiating to the latter but the latter fails to undergo PNT, a defect rescuable by exogenous Tfap2c. Our results link BMP4 to PNT through a binary logic of chromatin closing and opening, revealing the intrinsic power of extracellular factors to reorganize nuclear architecture in development.

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility [ChIP-Seq]

Project description:BMP4 regulates a plethora of developmental processes including dorsal-ventral axis and neural patterning. Here we report that BMP4 reconfigures nuclear archi-tecture during primed to naive transition (PNT). We first established a robust BMP4 driven PNT and shown by ATAC- and RNA-seq that it orchestrates the chromatin accessibility dynamics during PNT. Among the loci opened early by BMP4, we identified Zbtb7a/b as new targets that contribute to drive PNT. Mechanically, BMP first activates Zbtb7a/b in both chromatin and gene expression level, which in turn facilitate the opening of naïve pluripotent chromatin loci and allow the activation of naïve pluripotent genes. Surprisingly, Zbtb7a not only binds to chromatin loci near the genes to be activated, but also strategically occupies those to be silenced, thus resolving the conflicting role of BMP4 in both activating and suppressing gene ex-pression during PNT at the chromatin level. Our results reveal a previously un-known function of BMP4 in regulating nuclear architecture and link its targets Zbtb7a/b to chromatin remodeling and pluripotent fate control.

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Project description:Naive pluripotent cells in the implanting mouse blastocyst generate a rosette structure before undergoing lumenogenesis to form the egg cylinder. Simultaneously, they acquire primed pluripotency, the ability to differentiate into the primary germ layers. The existence of discrete intermediate pluripotent states during this transition has not been demonstrated. We identify here a distinct rosette pluripotent state, defined by co-expression of naive factors with transcription factor OTX2. Downregulation of WNT signals in the blastocyst drives transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells (RSCs), a self-renewing naive-primed intermediate. RSCs gain a unique epigenome that includes erasure of constitutive heterochromatin and bivalent marking of primed pluripotency genes. Notwithstanding this primed chromatin landscape, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate where control over pluripotency progression and morphogenesis pivots from WNT to MEK signals.

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BMP4 Resets Primed to Naive Pluripotency by Reprogramming Chromatin Accessibility

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

2020-06-16 | GSE122937 | GEO