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ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

ABSTRACT: ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

PROVIDER: PRJNA702795 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13738683.fastq.gz	Fastqsanger.gz
	SRR13738684.fastq.gz	Fastqsanger.gz
	SRR13738685.fastq.gz	Fastqsanger.gz
	SRR13738686.fastq.gz	Fastqsanger.gz
	SRR13738687.fastq.gz	Fastqsanger.gz

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ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

Project description:Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition remain largely unknown. NanoCAGE sequencing identified an evolutionarily conserved zinc finger repressor, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single cell RNA sequencing revealed that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 serves as a master repressor of human endogenous retrovirus H (HERVH). Active HERVH loci drive the expression of overlapping long non-coding RNAs (lncRNAs) whose downregulation by ZBTB12 is necessary for pluripotency exit and lineage derivation. Overall, we have identified a ZBTB12-HERVH-lncRNA axis as molecular machinery that safeguards the unidirectional transition of stem cell fates.

2021-06-30 | GSE118946 | GEO

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

Project description:Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition remain largely unknown. NanoCAGE sequencing identified an evolutionarily conserved zinc finger repressor, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single cell RNA sequencing revealed that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 cooperates with NANOG to fine-tune the expression of human endogenous retroviruses (HERVs). Active HERVH loci drive the expression of overlapping long non-coding RNAs (lncRNAs) whose downregulation by ZBTB12 is necessary for dedifferentiation blockage and pluripotency exit. Overall, we have identified a ZBTB12-HERVH-lncRNA axis as molecular machinery that safeguards the unidirectional transition of stem cell fates.

2022-05-31 | GSE167052 | GEO

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells [ChIP-seq]

Project description:Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition remain largely unknown. NanoCAGE sequencing identified an evolutionarily conserved zinc finger repressor, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single cell RNA sequencing revealed that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 cooperates with NANOG to fine-tune the expression of human endogenous retroviruses (HERVs). Active HERVH loci drive the expression of overlapping long non-coding RNAs (lncRNAs) whose downregulation by ZBTB12 is necessary for dedifferentiation blockage and pluripotency exit. Overall, we have identified a ZBTB12-HERVH-lncRNA axis as molecular machinery that safeguards the unidirectional transition of stem cell fates.

2022-12-26 | GSE205340 | GEO

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells [RNA-seq]

Project description:Development is generally viewed as one-way traffic of cell state transition from primitive to developmentally advanced states. However, molecular mechanisms that ensure the unidirectional transition remain largely unknown. NanoCAGE sequencing identified an evolutionarily conserved zinc finger repressor, ZBTB12, as a molecular barrier for dedifferentiation of human pluripotent stem cells (hPSCs). Single cell RNA sequencing revealed that ZBTB12 is essential for three germ layer differentiation by blocking hPSC dedifferentiation. Mechanistically, ZBTB12 cooperates with NANOG to fine-tune the expression of human endogenous retroviruses (HERVs). Active HERVH loci drive the expression of overlapping long non-coding RNAs (lncRNAs) whose downregulation by ZBTB12 is necessary for dedifferentiation blockage and pluripotency exit. Overall, we have identified a ZBTB12-HERVH-lncRNA axis as molecular machinery that safeguards the unidirectional transition of stem cell fates.

2022-12-26 | GSE205341 | GEO

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

Project description:ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells

| PRJNA487458 | ENA

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells

Project description:ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells

| PRJNA844540 | ENA

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells [ChIP-seq]

Project description:ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human stem cells [ChIP-seq]

| PRJNA844539 | ENA

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells [RNA-seq]

Project description:ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells [RNA-seq]

| PRJNA844544 | ENA

ZBTB12-HERVH-LncRNA axis is a molecular barrier for dedifferentiation of human pluripotent stem cells

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

2022-12-26 | GSE205342 | GEO

The lncRNA HERVH negatively regulates chromatin targeting and remodeling mediated by CHD7 [RNA-seq]

Project description:Chromodomain helicase DNA-binding protein 7 (Chd7) encodes an ATP-dependent chromatin remodeler required for normal human development. De novo mutations in CHD7 are the major cause of CHARGE syndrome which features multiple developmental defects. Previous studies have shown that CHD7 targets to specific genomic loci and alters local transcription potentially by remodeling the chromatin structure in a cell stage and lineage specific manner. We examined whether nuclear RNAs might contribute to its targeting and function. We used PAR-CLIP to identify a lncRNA, HERVH, that is uniquely expressed in pluripotent stem cells and preferentially interacts with CHD7. Knockdown of HERVH using LNAs or knockout of an individual copy of HERVH by CRISPR-Cas9 both resulted in increased binding of CHD7 and increased levels of H3K27ac at a subset of enhancers. Depletion of HERVH led to the activation of multiple genes, several of which might potentially poise cells towards differentiation. CHD7 bound HERVH RNA with high affinity but low specificity and that this interaction decreased the ability of CHD7 to bind and remodel nucleosomes. We present a model in which HERVH acts as a decoy to modulate the dynamics of CHD7 binding to enhancers in pluripotent cells and to prevent the activation of differentiation specific genes.

2021-10-10 | GSE171138 | GEO

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