Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Reversion to naïve human pluripotency creates a new methylation landscape devoid of blastocyst or germline memory

ABSTRACT: Human embryonic stem cells (hESCs) typically exhibit "primed" pluripotency, analogous to stem cells derived from the mouse post-implantation epiblast. This has led to a search for growth conditions that support self-renewal of hESCs akin to hypomethylated naïve epiblast cells in human pre-implantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naïve state or deriving a new hESC line under naïve conditions results in the establishment of Stage Specific Embryonic Antigen 4 (SSEA4) negative hESC lines with a transcriptional program resembling the human pre-implantation epiblast. In contrast, we discovered that the methylome of naïve hESCs in vitro is distinct from the human epiblast in vivo with loss of DNA methylation at primary imprints and a lost "memory" of the methylation state of the human oocyte. This failure to recover the naïve epiblast methylation landscape appears to be a consistent feature of self-renewing hypomethylated naïve hESCs in vitro.

ORGANISM(S): Homo sapiens

PROVIDER: GSE76970 | GEO | 2016/02/04

SECONDARY ACCESSION(S): PRJNA309166

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RRBS-seq data set)

Project description:Human embryonic stem cells (hESCs) can be captured in either a primed state resembling the post-implantation epiblast or in a naïve state resembling the pre-implantation epiblast. Naïve culture conditions allow study of pre-implantation development ex vivo but reportedly lead to chromosomal abnormalities, compromising their utility in research and potential therapeutic applications. Although MEK inhibition is essential for the naïve state, here we show that reduced MEK inhibition facilitates the establishment and maintenance of naïve hESCs that retain naïve-specific transcriptional and DNA methylation patterns yet accrue fewer chromosomal abnormalities. We further show that hESCs cultured under these modified conditions are less prone to apoptosis and proliferate more rapidly. Our results point to the importance of residual MAPK signaling and provide a simple modification to current protocols to enable robust growth and genomic stability in naïve hESCs.

2018-07-10 | GSE111018 | GEO

Reduced MEK inhibition confers a growth advantage and reduces genomic instability in naïve human ES cells (RNA-seq data set)

2018-07-10 | GSE110805 | GEO

Probing the signaling requirements for naïve human pluripotency by high-throughput chemical screening [RNA-seq]

Project description:Background: Naïve human embryonic stem cells (hESCs) have been isolated that more closely resemble the pre-implantation epiblast compared to conventional “primed” hESCs, but the signaling principles underlying these discrete stem cell states remain incompletely understood. Methods:Here we performed high-throughput screening using a library of >3,000 well-annotated compounds to identify essential signaling requirements for naïve human pluripotency. Results:We report that MEK1/2 inhibitors can be replaced during maintenance of naïve human pluripotency by inhibitors targeting either upstream (FGFR, RAF1) or downstream (ERK1/2) kinases. Naïve hESCs maintained under these alternative conditions display elevated levels of ERK phosphorylation but retain genome-wide DNA hypomethylation and a transcriptional identity of the pre-implantation epiblast. In contrast, dual inhibition of MEK and ERK promotes efficient primed-to-naïve resetting in combination with PKC, ROCK, and TNKS inhibitors and Activin A. Conclusions: This work demonstrates that induction and maintenance of naïve human pluripotency are governed by distinct signaling requirements.

2021-06-15 | GSE153212 | GEO

Probing the signaling requirements for naïve human pluripotency by high-throughput chemical screening [WGBS]

2021-06-15 | GSE153213 | GEO

PRODH regultes naive pluripotency by influencing mitochondrial oxidative phosphorylation (Targeted metabolomics)

Project description:Naïve human embryonic stem cells (hESCs) that resemble the pre-implantation epiblasts are fueled by a combination of aerobic glycolysis and oxidative phosphorylation, but their mitochondrial regulators are poorly understood. Here we report that, proline dehydrogenase (PRODH), a mitochondria-localized proline metabolism enzyme, is dramatically upregulated in naïve hESCs compared to their primed counterparts. The upregulation of PRODH is induced by a reduction in c-Myc expression that is dependent on PD0325901, a MEK inhibitor routinely present in naive hESC culture media. PRODH knockdown in naive hESCs significantly promoted mitochondrial oxidative phosphorylation (mtOXPHOS) and reactive oxygen species (ROS) production that triggered autophagy, DNA damage, and apoptosis. Remarkably, MitoQ, a mitochondria-targeted antioxidant, effectively restored the pluripotency and proliferation of PRODH-knockdown naïve hESCs, indicating that PRODH maintains naïve pluripotency by preventing excessive ROS production. Concomitantly, PRODH knockdown significantly slowed down the proteolytic degradation of multiple key mitochondrial electron transport chain complex proteins. Thus, we revealed a crucial role of PRODH in limiting mtOXPHOS and ROS production, and thereby safeguarding naïve pluripotency of hESCs. Targeted metabolomics (amino acids and derivatives) - H9P (Primed) VS H9N (Naïve) - is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7832' rel='noopener noreferrer' target='_blank'>MTBLS7832</a>.Untargeted metabolomics - H9N PLKO.1 vs H9P PLKO.1 / H9P shPRODH vs H9P PLKO.1 / H9N shPRODH vs H9N PLKO.1 - is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7840' rel='noopener noreferrer' target='_blank'>MTBLS7840</a>.

2024-02-12 | MTBLS7832 | MetaboLights

PRODH regultes naive pluripotency by influencing mitochondrial oxidative phosphorylation (Untargeted metabolomics)

Project description:Naïve human embryonic stem cells (hESCs) that resemble the pre-implantation epiblasts are fueled by a combination of aerobic glycolysis and oxidative phosphorylation, but their mitochondrial regulators are poorly understood. Here we report that, proline dehydrogenase (PRODH), a mitochondria-localized proline metabolism enzyme, is dramatically upregulated in naïve hESCs compared to their primed counterparts. The upregulation of PRODH is induced by a reduction in c-Myc expression that is dependent on PD0325901, a MEK inhibitor routinely present in naive hESC culture media. PRODH knockdown in naive hESCs significantly promoted mitochondrial oxidative phosphorylation (mtOXPHOS) and reactive oxygen species (ROS) production that triggered autophagy, DNA damage, and apoptosis. Remarkably, MitoQ, a mitochondria-targeted antioxidant, effectively restored the pluripotency and proliferation of PRODH-knockdown naïve hESCs, indicating that PRODH maintains naïve pluripotency by preventing excessive ROS production. Concomitantly, PRODH knockdown significantly slowed down the proteolytic degradation of multiple key mitochondrial electron transport chain complex proteins. Thus, we revealed a crucial role of PRODH in limiting mtOXPHOS and ROS production, and thereby safeguarding naïve pluripotency of hESCs. Untargeted metabolomics - H9N PLKO.1 vs H9P PLKO.1 / H9P shPRODH vs H9P PLKO.1 / H9N shPRODH vs H9N PLKO.1 - is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS7840' rel='noopener noreferrer' target='_blank'>MTBLS7840</a>.Targeted metabolomics (amino acids and derivatives) - H9P (Primed) VS H9N (Naïve) - is reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS7832' rel='noopener noreferrer' target='_blank'>MTBLS7832</a>.

2024-02-12 | MTBLS7840 | MetaboLights

Novel culture conditions facilitating the induction of naïve pluripotency in human embryonic stem cells

Project description:It is now well recognized that human embryonic stem cells (hESCs)1 closely resemble mouse epiblast stem cells (mEpiSCs)2-5 exhibiting primed pluripotency unlike mouse ESCs (mESCs) which acquire a naïve pluripotent state4-8. Efforts have been made to trigger naïve pluripotency in hESCs9-11 for subsequent unbiased lineage-specific differentiation, a common conundrum faced by primed pluripotent hESCs due to heterogeneity in gene expression existing within and between hESC lines12. We report here a novel culture medium facilitating rapid induction of naïve pluripotency in established hESCs. Our medium also allows derivation of naïve mESCs from blastocyst stage which has not been shown earlier. The established naïve hESCs could survive long-term single cell passaging, maintain a normal karyotype, exhibit upregulation of naïve pluripotency genes and were dependent on signaling pathways similar to naïve mESCs. Also, they undergo global DNA demethylation, cluster together with previously described naïve hESCs13 and show a distinctive long non-coding RNA profile. Collectively, we demonstrate an alternate route to capture naïve pluripotency in hESCs which is fast, reproducible, can be employed to derive naïve mESCs and can induce efficient differentiation. Three primed and matching naive human embryonic stem cell lines were profiled in duplo.

2015-06-08 | E-GEOD-57271 | biostudies-arrayexpress

Untargeted histone profiling of human embryonic stem cell conversion over time reveals fundamental epigenetic changes between pluripotent and naive states

Project description:Recently, various groups managed to isolate naïve human embryonic stem cell (hESC) state in vitro has come into acceptance. However, a thorough epigenetic characterization of this human ground state, defined as a state without any epigenetic restrictions, and how that compares to mouse is currently lacking. Also, the epigenomic remodeling required to obtain the ground state, and the important transient processes occurring during the remodeling, have remained elusive in human. Here, we address these issues by using an untargeted mass spectrometry-based (MS) approach to profile the histone epigenome in a time-resolved experimental design. Special care was given to defining the naïve hESC state that was reached over 12 passages (P12, 37 days) in feeder-free conditions in this study. We found that conversion is a multi-staged process with a prominent cellular disturbance after stimulation (P3), an increase in cell proliferation between P3 and P6 and a naïve cell state stabilizing between P9 and P12. In total, 20 different histone post-translational modifications (hPTMs) changed significantly over time from primed to naïve hESCs. Most notably, H3K27me3 is the most prominently increasing hPTM in naïve hESCs, in line with what we recently described in mouse. Essentially, we present a first roadmap of the changing human histone epigenome from primed to naïve state and emphasize that the overlap with mouse hints at a conserved Mammalian epigenetic signature of the ground state.

2019-11-27 | PXD013067 | Pride

Novel culture conditions facilitating the induction of naïve pluripotency in human embryonic stem cells

2015-06-08 | GSE57271 | GEO

Transcriptional landscape changes during human embryonic stem cell derivation

Project description:Currently, there is only minimal information elucidating the transcriptional changes occurring during the in vitro transition of the inner cell mass (ICM) towards the human embryonic stem cell (hESC) stage and the role played by the post inner cell mass intermediate (PICMI). In this study, we perform in-depth analysis of the transcriptional heterogeneity between these three stages of hESC derivation in order to correlate their downstream effects on pluripotency states and differentiation. We reveal that although PICMI is transcriptionally in close proximity to the hESC profile and distinct from ICM, it exhibits upregulation of primordial germ cell markers, dependence on LIF signaling, upregulation of naïve pluripotency-specific signaling networks and appears to be a switching point from naïve to primed pluripotency. This indicates similarities with mouse epiblast-like cells displaying a transient state of pluripotency, between naïve and primed pluripotent states. Overall, we highlight the need to gain insight into the molecular and transcriptional landscape during hESC derivation, which will further help in the derivation of human PGCs and naïve hESCs in vitro which remains inefficient.

2018-09-24 | GSE119378 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data