Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA407255 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6037391.fastq.gz | Fastqsanger.gz | |||
| SRR6037401.fastq.gz | Fastqsanger.gz | |||
| SRR6037383.fastq.gz | Fastqsanger.gz | |||
| SRR6037393.fastq.gz | Fastqsanger.gz | |||
| SRR6037403.fastq.gz | Fastqsanger.gz |
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Project description:<p>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.</p><p><br></p><p><strong>Targeted metabolomics</strong> (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'><strong>MTBLS7832</strong></a>.</p><p><strong>Untargeted metabolomics</strong> - 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'><strong>MTBLS7840</strong></a>.</p>
2024-02-12 | MTBLS7832 | MetaboLights
Project description:<p>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.</p><p><br></p><p><strong>Untargeted metabolomics</strong> - 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'><strong>MTBLS7840</strong></a>.</p><p><strong>Targeted metabolomics</strong> (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'><strong>MTBLS7832</strong></a>.</p>
2024-02-12 | MTBLS7840 | MetaboLights
Project description:Whole proteome profiling and quantification was performed on an isogenic Huntington disease (IsoHD) human embryonic stem cell (hESC) allelic panel. The IsoHD hESCs harbour 30, 45, 65 and 81 CAG repeats in the first exon of HTT. Whole proteome quantification was also performed on neural progenitor cells derived from the IsoHD hESC panel.
2019-02-14 | PXD006585 | JPOST Repository
Project description:N6-methyladenosine (m6A) is the most abundant chemical modification in mRNA, and plays important roles in human embryonic stem cell pluripotency, maintenance, and differentiation. However, the role of m6A and the precise mechanisms involved during the development of β-cells are unexplored. Here, we explored the requirement of METTL14-mediated m6A RNA methylome in human embryonic stem cell (hESC) differentiation by simultaneously inducing METTL14 knockdown in H1 and MEL1 hESCs with doxycycline (Dox) treatment and differentiating hESCs towards the three embryonic germ layers using embryoid body (EB) formation assays.
2024-07-01 | GSE236322 | GEO
Project description:The realization of human embryonic stem cells (hESC) as a model for human developmental hematopoiesis and potential cell replacement strategies relies on an improved understanding of the extrinsic and intrinsic factors regulating hematopoietic-specific hESC differentiation. Mesenchymal stem cells (hMSCs) are multipotent cells of mesodermal origin that form part of hematopoietic stem cell niches and have an important role in the regulation of hematopoiesis through production of secreted factors and/or cell-to-cell interactions. We have previously shown that hESCs may be successfully maintained feeder-free using hMSC-conditioned media (MSC-CM). Here, we hypothesized that hESCs maintained in MSC-CM may be more prone to differentiation towards hematopoietic lineage than hESCs grown in standard human foreskin fibroblast (HFF)-conditioned media (HFF-CM). We report that specification into hemogenic progenitors and subsequent hematopoietic differentiation and clonogenic progenitor capacity is robustly enhanced in hESC lines maintained in MSC-CM. Interestingly, co-culture of hESCs on hMSCs fully abrogates hematopoietic specification of hESCs suggesting that the improved hematopoietic differentiation is mediated by MSC-secreted factors rather than by MSC-hESC physical interactions. To investigate the molecular mechanism involved in this process, we analyzed global (LINE-1) methylation and genome-wide promoter DNA methylation. Human ESCs grown in MSC-CM showed a decrease of 20% in global DNA methylation and a promoter DNA methylation signature consisting in 45 genes commonly hypomethylated and 102 genes frequently hypermethylated. Our data indicate that maintenance of hESCs in MSC-CM robustly augments hematopoietic specification and that the process seems mediated by MSC-secreted factors conferring a DNA methylation signature to undifferentiated hESCs which may influence further predisposition towards hematopoietic specification. Total DNA isolated by standard procedures from human embryonic stem cells (hESC) cultured in different conditioned media
2011-10-02 | E-GEOD-30456 | biostudies-arrayexpress
Project description:The maintenance of pluripotency requires the coordinated expression of a set of essential genes. Thorough identification of these genes is vital for gaining a better understanding of the pluripotent state. To this end, we have recently generated a genome-wide loss-of-function library in haploid human pluripotent stem cells utilizing the bacterial clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology using nearly 180,000 single guide RNAs (sgRNAs) and targeting 18,166 protein-coding genes. By combining the results of our high-throughput genetic screening with the analysis of publicly available RNAseq data of pluripotent stem cells and several somatic cells, we have determined the essential genes which have an enriched expression in hESCs and termed these genes as hESC-essential genes. Here, we have individually knocked down four of these hESC-essential genes with siRNAs, namely SALL4, DSCC1, SEPHS1 and VRTN, in human embryonic stem cells and analyzed the transcriptomes of the cells upon downregulation of these transcripts in order to unravel part of the pathways affected by hESC-essential genes.
2018-04-30 | GSE103846 | GEO
Project description:Transcription factors are key determinants of lineage commitment during mammalian development. However, the function and molecular mechanism for the transcription factors in the formation of three primary germ layers during human embryonic development are not fully elucidated. Here, we report that homeobox-containing transcription factor HESX1 plays a critical role in mesendodermal (ME) commitment of human embryonic stem cells (hESCs). Our results show that expression of HESX1 in hESCs is regulated by OCT4 and NANOG, and that its expression level changes with hESC differentiation. We find that knockdown of HESX1 does not disrupt the undifferentiated state of hESCs, in terms of cell morphology and expression levels of pluripotency- associated genes. However, HESX1 deficiency in hESCs impairs their ME commitment, whereas forced expression of HESX1 significantly enhances ME marker expression during ME commitment. Interestingly, HESX1 knockdown in hESCs represses ERK1/2 signaling activated by ME induction, while overexpression of HESX1 markedly enhances ERK1/2 activity during ME commitment of hESCs. Of note, MEK inhibitor PD0325901 weakens or even eliminates HESX1 overexpression- mediated promotive effects on ME induction in a dosage- dependent manner. Together, this study identifies a novel role of HESX1 in hESC commitment to ME cells and establishes the functional link between a transcription factor and lineage- associated signaling. These findings would help to better understand early human development and develop more efficient protocols to induce hESC differentiation to desired lineages.
2022-06-10 | GSE199196 | GEO
Project description:While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis. This proteomics dataset contains the data from co-immunopreciptation experiments using CSDE1 antibody in hESCs
2018-05-16 | PXD007271 | Pride
Project description:ELABELA (ELA) is a peptide hormone required for heart development that signals via the Apelin Receptor (APLNR, APJ). ELA is also abundantly secreted by human embryonic stem cells (hESCs), which do not express APLNR. Here we show that ELA signals in a paracrine fashion in hESCs to maintain self-renewal. ELA inhibition by CRISPR/Cas9-mediated deletion, shRNA or neutralizing antibodies causes reduced hESC growth, cell death and loss of pluripotency. Global phosphoproteomic and transcriptomic analyses of ELA-pulsed hESCs show that it activates PI3K/AKT/mTORC1 signaling required for cell survival. ELA promotes hESC cell cycle progression and protein translation, and blocks stress-induced apoptosis. INSULIN and ELA have partially overlapping functions in hESC medium, but only ELA can potentiate the TGFβ pathway to prime hESCs towards the endoderm lineage. We propose that ELA, acting through an alternate cell-surface receptor, is an endogenous secreted growth factor in human embryos and hESCs that promotes growth and pluripotency. Global Transcriptomic Analysis of INSULIN versus ELA-pulsed human embryonic stem cells was performed to elucidate the functional overlap between these two ligands
2015-09-20 | E-GEOD-71949 | biostudies-arrayexpress
Project description:We compared hESCs with their neuronal counterpart to quantify differences in the expression of cold-shock domain containing proteins. While the transcriptional network of human embryonic stem cells (hESCs) has been extensively studied, relatively little is known about how post-transcriptional modulations determine hESC function. RNA-binding proteins play central roles in RNA regulation, including translation and turnover. Here we show that the RNA-binding protein CSDE1 is highly expressed in hESCs to maintain their undifferentiated state and prevent default neural fate. Notably, loss of CSDE1 accelerates neural differentiation and potentiates neurogenesis. Conversely, ectopic expression of CSDE1 impairs neural differentiation. We find that CSDE1 post-transcriptionally modulates core components of multiple regulatory nodes of hESC identity, neuroectoderm commitment and neurogenesis. Among these key pro-neural/neuronal factors, CSDE1 binds fatty acid binding protein 7 (FABP7) and vimentin (VIM) mRNAs as well as transcripts involved in neuron projection development regulating their stability and translation. Thus, our results uncover CSDE1 as a central post-transcriptional regulator of hESC identity and neurogenesis.
2018-05-16 | PXD007738 | Pride