WDR36 regulates trophectoderm differentiation during human preimplantation embryonic development through glycolytic metabolism
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1156759 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30561376_1.fastq.gz | Fastqsanger.gz | |||
| SRR30561376_2.fastq.gz | Fastqsanger.gz | |||
| SRR30561377_1.fastq.gz | Fastqsanger.gz | |||
| SRR30561377_2.fastq.gz | Fastqsanger.gz | |||
| SRR30561378_1.fastq.gz | Fastqsanger.gz |
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Project description:Mammalian pre-implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory functions in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell-derived blastocyst-like structure, termed a blastoid, offer an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, we further demonstrated that WDR36 interference could block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein LDHA, thereby positively regulating glycolysis during the late stage of human blastoid development. Taken together, our study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.
2025-04-02 | GSE276344 | GEO
Project description:Mammalian pre-implantation development is a complex process involving sophisticated regulatory dynamics. WD repeat domain 36 (WDR36) is known to play a critical role in mouse early embryonic development, but its regulatory function in human embryogenesis is still elusive due to limited access to human embryos. The human pluripotent stem cell-derived blastocyst-like structure, termed a blastoid, offers an alternative means to study human development in a dish. In this study, after verifying that WDR36 inhibition disrupted polarization in mouse early embryos, it is further demonstrated that WDR36 interference can block human blastoid formation, dominantly hindering the trophectoderm lineage commitment. Both transcriptomics and targeted metabolomics analyses revealed that WDR36 interference downregulated glucose metabolism. WDR36 can interact with glycolytic metabolic protein lactate dehydrogenase A (LDHA), thereby positively regulating glycolysis during the late stage of human blastoid formation. Taken together, the study has established a mechanistic connection between WDR36, glucose metabolism, and cell fate determination during early embryonic lineage commitment, which may provide potential insights into novel therapeutic targets for early adverse pregnancy interventions.
| S-EPMC11791977 | biostudies-literature
Project description:Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect global histone methylation levels; rather, it decreases acetyl-CoA availability, reduces histone acetyltransferase activity and weakens the pluripotency network. We propose that metabolism functions as a positive feedback loop aiding in trophectoderm fate induction and maturation, highlighting that global metabolic rewiring can promote specificity in cell fate decisions through intricate regulation of signalling and chromatin.
2025-02-27 | GSE247630 | GEO
Project description:Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect global histone methylation levels; rather, it decreases acetyl-CoA availability, reduces histone acetyltransferase activity and weakens the pluripotency network. We propose that metabolism functions as a positive feedback loop aiding in trophectoderm fate induction and maturation, highlighting that global metabolic rewiring can promote specificity in cell fate decisions through intricate regulation of signalling and chromatin.
2025-02-27 | GSE247631 | GEO
Project description:Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect global histone methylation levels; rather, it decreases acetyl-CoA availability, reduces histone acetyltransferase activity and weakens the pluripotency network. We propose that metabolism functions as a positive feedback loop aiding in trophectoderm fate induction and maturation, highlighting that global metabolic rewiring can promote specificity in cell fate decisions through intricate regulation of signalling and chromatin.
2025-02-27 | GSE247633 | GEO
Project description:Development and lineage choice are driven by interconnected transcriptional, epigenetic and metabolic changes. Specific metabolites, such as α-ketoglutarate (αKG), function as signalling molecules affecting the activity of chromatin-modifying enzymes. However, how metabolism coordinates cell-state changes, especially in human pre-implantation development, remains unclear. Here we uncover that inducing naive human embryonic stem cells towards the trophectoderm lineage results in considerable metabolic rewiring, characterized by αKG accumulation. Elevated αKG levels potentiate the capacity of naive embryonic stem cells to specify towards the trophectoderm lineage. Moreover, increased αKG levels promote blastoid polarization and trophectoderm maturation. αKG supplementation does not affect global histone methylation levels; rather, it decreases acetyl-CoA availability, reduces histone acetyltransferase activity and weakens the pluripotency network. We propose that metabolism functions as a positive feedback loop aiding in trophectoderm fate induction and maturation, highlighting that global metabolic rewiring can promote specificity in cell fate decisions through intricate regulation of signalling and chromatin.
2025-02-27 | GSE270957 | GEO
Project description:The balance between glycolytic and oxidative metabolism shifts during differentiation of human embryonic stem cells (hESCs) and during reprogramming of somatic cells into pluripotent stem cells. However the contribution of glycolytic metabolism to various stages of pluripotency is not well understood. Additionally, few tools have been developed that modulate pluripotent stem cell glycolytic metabolism to influence self-renewal or differentiation. Here we show that the degree of human pluripotency is associated with glycolytic rate, whereby naive hESCs exhibit higher glycolytic flux, increased MYC transcriptional activity, and elevated nuclear N-MYC levels relative to primed hESCs. Consistently, the inner cell mass of human blastocysts also exhibits increased MYC transcriptional activity relative to primed hESCs and elevated nuclear N-MYC levels. Expression of the lactate transporter, monocarboxylate transporter 1 (MCT1), is strongly associated with the pluripotent state, and reduction of glycolysis using a small molecule inhibitor towards MCT1 decreases self-renewal of naïve hESCs and feeder-free cultured primed hESCs, but not that of primed hESCs grown in feeder-supported conditions. Lastly, reduction of glycolytic metabolism via MCT1 inhibition in feeder-free primed hESCs enhances neural lineage specification. These findings validate the association between glycolytic metabolism and pluripotency, reveal differences in the glucose metabolism of feeder- versus feeder-free cultured hESCs, and show that pharmacologic regulation of glycolysis can influence self-renewal and initial cell fate specification of human pluripotent stem cells.
2016-08-16 | GSE83491 | GEO
Project description:Tead4 is a critical transcription factor expressed during preimplantation development and is essential for the expression of trophectoderm-specific genes in mice. However, the mechanism of Tead4’s function in mouse preimplantation development and its conservation across mammals remains unclear. Here, we report that Tead4 is a crucial transcription factor necessary for blastocyst formation in mice. Disruption of TEAD4 through base editing results in developmental arrest at the morula stage. Additionally, RNA-seq analysis reveals dysregulation of 670 genes in Tead4 knockout embryos. As anticipated, Tead4 knockout leads to a decrease in trophectoderm genes CDX2 and GATA3. Intriguingly, we observed a reduction in KRT8, suggesting that Tead4 influences the integrity of the trophectoderm epithelium in mice. More importantly, we noted a decrease in nuclear YAP for Tead4-deficient embryos, indicating that Tead4 directly regulates Hippo signaling. In contrast, bovine embryos with TEAD4 depletion can still develop to blastocysts with normal expression of CDX2, GATA3, and SOX2, albeit with a decrease in total cell number and ICM cell number. In conclusion, we propose that Tead4 regulates mouse blastocyst formation via Krt8 and Yap, both of which are critical regulators of mouse preimplantation development.
2024-07-15 | GSE237418 | GEO
Project description:Profiles of H3K4me3, H3K27ac, H3K27me3 and H3K9me3 in bovine GV oocytes and preimplantation embryos, and the characterization of chromatin accessibility in bovine blastocyst, inner cell mass and trophectoderm.
2023-02-16 | GSE193640 | GEO
Project description:Ageing is a crucial factor that affects embryonic development and implantation. Maternal age has an impact on the blastocyst's gene expression levels from the fertilised oocyte and throughout the development of the preimplantation embryo. The current study reported differential gene expression analysis among trophectoderm samples that derived from young maternal age women (YMA - below 30 years), intermediate maternal age (IMA - 30-39 years old) and advanced maternal age women (AMA - at least 40 years old). The molecular approach was assayed by a low-input next generation RNA sequencing approach. Hundreds of significantly differentially expressed transcripts were reported. Extracellular exosome-related transcripts were significantly higher in the trophectoderm cells that derived from young women. According to our analysis, several important transcripts were reported. These molecular biomarkers may have a potential role in embryonic-endometrial communication and could be used in a diagnostic setting, that could help to improve the blastocyst implantation potential.
2021-07-20 | GSE133592 | GEO