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Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [RNA-seq]

ABSTRACT: Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [RNA-seq]

PROVIDER: PRJNA859153 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20229439_1.fastq.gz	Fastqsanger.gz
	SRR20229439_2.fastq.gz	Fastqsanger.gz
	SRR20229440_1.fastq.gz	Fastqsanger.gz
	SRR20229440_2.fastq.gz	Fastqsanger.gz
	SRR20229441_1.fastq.gz	Fastqsanger.gz

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Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [methArray]

Project description:Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [methArray]

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Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [miRNA-seq]

Project description:Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [miRNA-seq]

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Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [methArray]

Project description:A detailed understanding of the developmental substates of human pluripotent stem cells (hPSCs) is needed to optimize their use in cell therapy and models of early development. Genetic instability and risk of tumorigenicity of primed hPSCs are well documented, but a systematic isogenic comparison between primed and naive substates has not been previously performed. We derived four hESC lines in naïve conditions and generated isogenic pairs of naïve and primed cultures. Through phenotypic, mRNA, miRNA, and DNA methylation profiling, we identified changes that arose during the naïve-primed transition and over extended culture. Although early naïve hESC cultures showed greater proliferation and clonogenic potential compared to primed cultures, they drifted toward a more primed-like substate over time, including accumulation of genetic abnormalities. Overall, we show that transcriptomic and epigenomic profiling can be used to place naïve/primed cultures along a developmental continuum, and may inform their utility for clinical and research applications.

2022-11-03 | GSE208299 | GEO

Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [miRNA-seq]

2022-11-03 | GSE208301 | GEO

Stabilization of virgin naïve hESCs in two distinct substates along the continuum of pluripotency [RNA-seq]

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Stabilization of hESCs in two distinct substates along the continuum of pluripotency.

Project description:A detailed understanding of the developmental substates of human pluripotent stem cells (hPSCs) is needed to optimize their use in cell therapy and for modeling early development. Genetic instability and risk of tumorigenicity of primed hPSCs are well documented, but a systematic isogenic comparison between substates has not been performed. We derived four hESC lines in naive human stem cell medium (NHSM) and generated isogenic pairs of NHSM and primed cultures. Through phenotypic, transcriptomic, and methylation profiling, we identified changes that arose during the transition to a primed substate. Although early NHSM cultures displayed naive characteristics, including greater proliferation and clonogenic potential compared with primed cultures, they drifted toward a more primed-like substate over time, including accumulation of genetic abnormalities. Overall, we show that transcriptomic and epigenomic profiling can be used to place human pluripotent cultures along a developmental continuum and may inform their utility for clinical and research applications.

| S-EPMC9668692 | biostudies-literature

Stabilization of hESCs in two distinct substates along the continuum of pluripotency

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

2022-11-03 | GSE208302 | GEO

Project description:Stabilization of hESCs in two distinct substates along the continuum of pluripotency

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Comparison non-targeting hRNA hESCs versus UBE2K shRNA hESCs

Project description:Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. When compared with their differentiated counterparts, immortal human embryonic stem cells (hESCs) have a unique chromatin architecture and low levels of trimethylated histone H3 at lysine 9 (H3K9me3), a heterochromatin-associated modification. Here we assess a link between the intrinsic epigenetic landscape and ubiquitin-proteasome system of hESCs. We find that hESCs exhibit high expression of UBE2K, a ubiquitin-conjugating enzyme. Loss of UBE2K increases the levels of H3K9 trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation. Concomitantly, loss of UBE2K impairs the ability of hESCs to differentiate into neural progenitors with neurogenic properties. Besides H3K9 trimethylation, we find that UBE2K binds histone H3 to induce its polyubiquitination and degradation by the proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates both histone H3 levels and H3K9 trimethylation in C. elegans germline. Thus, our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells.

2020-06-01 | PXD018625 | Pride

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