Metabolic rewiring underpins human trophoblast induction [scRNA-Seq 2D]
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ABSTRACT:
PROVIDER: PRJNA1039846 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metabolic rewiring underpins human trophoblast induction
| PRJNA1039841 | ENA
Project description:Metabolic rewiring underpins human trophoblast induction [ATAC-Seq]
| PRJNA1039843 | ENA
Project description:Metabolic rewiring underpins human trophoblast induction [RNA-Seq]
| PRJNA1039845 | ENA
Project description:Metabolic rewiring underpins human trophoblast induction [scRNA-Seq 3D]
| PRJNA1129112 | ENA
Project description:Development is driven by a sequence of molecularly interconnected transcriptional, epigenetic, and metabolic changes. Specific metabolites, like α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin modifying enzymes. It remains unclear, how such non-canonical function of metabolism coordinates specific cell-state changes especially in early development. Here we uncover that when naive human embryonic stem cells (nESC) are induced towards human trophoblast stem cells (hiTSC) a significant metabolic rewiring occurs, characterised by the accumulation of αKG. In vivo transcriptomic data further confirmed that metabolic rewiring likely takes place in the nascent trophectoderm (TE). We show that the intracellular αKG level is an important regulator of TE fate acquisition. Indeed, a dimethyl-αKG (dm-αKG) treatment of nESC increases their competence towards TE-like cells during hiTSC induction. Moreover, dm-αKG also increased the robustness of blastoid polarisation, marking the first step of TE induction. Surprisingly, dm-αKG treatment does not affect global histone methylation levels in nESC, but rather leads to decreased H3K27ac and weakening of the pluripotency network. Further functional assays confirmed that both reduced histone acetyltransferase activity and increased αKG level promote nESC competence towards TE-lineage but not extraembryonic mesoderm. We propose that an increased αKG level regulates pluripotency through deacetylation, thus creating a positive feedback loop promoting the induction of TE fate.
2025-02-27 | GSE247633 | GEO
Project description:Development is driven by a sequence of molecularly interconnected transcriptional, epigenetic, and metabolic changes. Specific metabolites, like α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin modifying enzymes. It remains unclear, how such non-canonical function of metabolism coordinates specific cell-state changes especially in early development. Here we uncover that when naive human embryonic stem cells (nESC) are induced towards human trophoblast stem cells (hiTSC) a significant metabolic rewiring occurs, characterised by the accumulation of αKG. In vivo transcriptomic data further confirmed that metabolic rewiring likely takes place in the nascent trophectoderm (TE). We show that the intracellular αKG level is an important regulator of TE fate acquisition. Indeed, a dimethyl-αKG (dm-αKG) treatment of nESC increases their competence towards TE-like cells during hiTSC induction. Moreover, dm-αKG also increased the robustness of blastoid polarisation, marking the first step of TE induction. Surprisingly, dm-αKG treatment does not affect global histone methylation levels in nESC, but rather leads to decreased H3K27ac and weakening of the pluripotency network. Further functional assays confirmed that both reduced histone acetyltransferase activity and increased αKG level promote nESC competence towards TE-lineage but not extraembryonic mesoderm. We propose that an increased αKG level regulates pluripotency through deacetylation, thus creating a positive feedback loop promoting the induction of TE fate.
2025-02-27 | GSE247631 | GEO
Project description:Development is driven by a sequence of molecularly interconnected transcriptional, epigenetic, and metabolic changes. Specific metabolites, like α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin modifying enzymes. It remains unclear, how such non-canonical function of metabolism coordinates specific cell-state changes especially in early development. Here we uncover that when naive human embryonic stem cells (nESC) are induced towards human trophoblast stem cells (hiTSC) a significant metabolic rewiring occurs, characterised by the accumulation of αKG. In vivo transcriptomic data further confirmed that metabolic rewiring likely takes place in the nascent trophectoderm (TE). We show that the intracellular αKG level is an important regulator of TE fate acquisition. Indeed, a dimethyl-αKG (dm-αKG) treatment of nESC increases their competence towards TE-like cells during hiTSC induction. Moreover, dm-αKG also increased the robustness of blastoid polarisation, marking the first step of TE induction. Surprisingly, dm-αKG treatment does not affect global histone methylation levels in nESC, but rather leads to decreased H3K27ac and weakening of the pluripotency network. Further functional assays confirmed that both reduced histone acetyltransferase activity and increased αKG level promote nESC competence towards TE-lineage but not extraembryonic mesoderm. We propose that an increased αKG level regulates pluripotency through deacetylation, thus creating a positive feedback loop promoting the induction of TE fate.
2025-02-27 | GSE247630 | GEO
Project description:Development is driven by a sequence of molecularly interconnected transcriptional, epigenetic, and metabolic changes. Specific metabolites, like α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin modifying enzymes. It remains unclear, how such non-canonical function of metabolism coordinates specific cell-state changes especially in early development. Here we uncover that when naive human embryonic stem cells (nESC) are induced towards human trophoblast stem cells (hiTSC) a significant metabolic rewiring occurs, characterised by the accumulation of αKG. In vivo transcriptomic data further confirmed that metabolic rewiring likely takes place in the nascent trophectoderm (TE). We show that the intracellular αKG level is an important regulator of TE fate acquisition. Indeed, a dimethyl-αKG (dm-αKG) treatment of nESC increases their competence towards TE-like cells during hiTSC induction. Moreover, dm-αKG also increases the robustness of blastoid polarisation and TE maturation. Surprisingly, dm-αKG treatment does not affect global histone methylation levels in nESC, but rather leads to decreased histone acetyltransferase (HAT) activity and weakening of the pluripotency network. Further functional assays confirmed that both reduced histone acetyltransferase activity and increased αKG level promote nESC competence towards TE-lineage but not primitive endoderm. We propose that an increased αKG level regulates pluripotency through deacetylation, thus creating a positive feedback loop promoting the induction of TE fate.
2025-02-27 | GSE270957 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2025-02-27 | GSE247634 | GEO
Project description:Human naive pluripotent stem cells have unrestricted lineage potential. Underpinning this property, naive cells are thought to lack chromatin-based lineage barriers. However, this assumption has not been tested. Here, we define the chromatin-associated proteome, histone post-translational modifications and transcriptome of human naive and primed pluripotent stem cells. Our integrated analysis reveals differences in the relative abundance and activities of distinct chromatin modules. We identify a strong enrichment of Polycomb Repressive Complex 2 (PRC2)-associated H3K27me3 in naive pluripotent stem cell chromatin, and H3K27me3 enrichment at promoters of lineage-determining genes, including trophoblast regulators. PRC2 activity acts as a chromatin barrier restricting the differentiation of naive cells towards the trophoblast lineage, while inhibition of PRC2 promotes trophoblast fate induction and cavity formation in human blastoids. Together, our results establish that human naive pluripotent stem cells are not epigenetically unrestricted, but instead possess chromatin mechanisms that oppose the induction of alternative cell fates.
2022-05-09 | PXD032792 | Pride