Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1240850 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32829628_1.fastq.gz | Fastqsanger.gz | |||
| SRR32829628_2.fastq.gz | Fastqsanger.gz | |||
| SRR32829629_1.fastq.gz | Fastqsanger.gz | |||
| SRR32829629_2.fastq.gz | Fastqsanger.gz | |||
| SRR32829630_1.fastq.gz | Fastqsanger.gz |
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Project description:Human naïve pluripotent stem cells (nPSCs) can be indued by various combinations of signaling factors to genearte blastocyst-like structures known as blastoids. Despite the rapid advances in human blastoid models, their potential to uncover fundamental mechanisms of early development remains limited, leaving key morphogenetic processes poorly understood. Here, we present a simple and robust system in which dimethyl sulfoxide (DMSO) alone induces blastoid formation from human nPSCs. This model faithfully recapitulates pre- and post-implantation features, including amniotic cavity formation, and reveals a previously unrecognized mechanism of trophectoderm (TE) cavitation. Using this system, we identified lysosome-related genes—particularly those encoding subunits of the proton pump V-ATPase—are essential for blastoid cavitation. DMSO treatment upregulates key V-ATPase subunits (ATP6V0A4 and ATP6V1B1), which are also enriched in the TE of human embryos. Inhibition of V-ATPase disrupted lysosomal acidification, blocked intracellular vacuole formation, and impaired blastoid cavitation. Furthermore, both genetic and pharmacological disruption of V-ATPase function significantly impaired cavitation in mouse and human blastocysts. Thus, our simple DMSO model recapitulates key aspects of human blastocyst development and reveals a conserved mechanism involving V-ATPase–mediated lysosomal acidification during early mammalian embryogenesis.
2026-03-11 | GSE316552 | GEO
Project description:Human naïve pluripotent stem cells (nPSCs) can be induced by various combinations of signaling factors to generate blastocyst-like structures, termed blastoids. Despite rapid progress in human blastoid models, their potential to uncover fundamental mechanisms of early human development remains limited, leaving key morphogenetic processes poorly understood. Here, we describe a simple and robust system in which dimethyl sulfoxide (DMSO) alone induces blastoid formation from human nPSCs. This model recapitulates key pre- and post-implantation features and exhibits enhanced polar trophectoderm (TE) organization, more efficient attachment within an implantation-relevant window, improved epiblast lumenogenesis associated with amniotic cavity formation, and more robust, sustained expansion of embryonic lineages following attachment. Using this system, we reveal a previously unrecognized mechanism underlying TE cavitation and identify lysosome-associated genes — particularly subunits of the proton pump V-ATPase — as essential regulators of blastoid cavitation. DMSO treatment upregulates key V-ATPase 2 subunits (ATP6V0A4 and ATP6V1B1), which are also enriched in the TE of human embryos. Genetic or pharmacological inhibition of V-ATPase activity disrupts lysosomal acidification, blocks intracellular vacuole formation, and impairs blastoid cavitation, whereas overexpression of V-ATPase subunits rescues this phenotype. Furthermore, genetic and pharmacological perturbations of V-ATPase function significantly compromise cavitation in both mouse and human blastocysts. Finally, DMSO treatment induces membrane biomechanical changes characteristic of early embryonic development, suggesting a mode of action distinct from conventional small-molecule, signaling pathway- based induction strategies. This simple DMSO-based blastoid model recapitulates key aspects of human blastocyst development and reveals a conserved requirement for V- ATPase-mediated lysosomal acidification during early mammalian embryogenesis.
2026-03-11 | GSE239744 | GEO
Project description:Human naïve pluripotent stem cells (nPSCs) can be induced by various combinations of signaling factors to generate blastocyst-like structures, termed blastoids. Despite rapid progress in human blastoid models, their potential to uncover fundamental mechanisms of early human development remains limited, leaving key morphogenetic processes poorly understood. Here, we describe a simple and robust system in which dimethyl sulfoxide (DMSO) alone induces blastoid formation from human nPSCs. This model recapitulates key pre- and post-implantation features and exhibits enhanced polar trophectoderm (TE) organization, more efficient attachment within an implantation-relevant window, improved epiblast lumenogenesis associated with amniotic cavity formation, and more robust, sustained expansion of embryonic lineages following attachment. Using this system, we reveal a previously unrecognized mechanism underlying TE cavitation and identify lysosome-associated genes — particularly subunits of the proton pump V-ATPase — as essential regulators of blastoid cavitation. DMSO treatment upregulates key V-ATPase 2 subunits (ATP6V0A4 and ATP6V1B1), which are also enriched in the TE of human embryos. Genetic or pharmacological inhibition of V-ATPase activity disrupts lysosomal acidification, blocks intracellular vacuole formation, and impairs blastoid cavitation, whereas overexpression of V-ATPase subunits rescues this phenotype. Furthermore, genetic and pharmacological perturbations of V-ATPase function significantly compromise cavitation in both mouse and human blastocysts. Finally, DMSO treatment induces membrane biomechanical changes characteristic of early embryonic development, suggesting a mode of action distinct from conventional small-molecule, signaling pathway- based induction strategies. This simple DMSO-based blastoid model recapitulates key aspects of human blastocyst development and reveals a conserved requirement for V- ATPase-mediated lysosomal acidification during early mammalian embryogenesis.
2026-03-11 | GSE236961 | GEO
Project description:The developmental biology of limb synovial joints and their water/lubricant-filled cavity remains unclear. Joint formation is known to start with emergence at each prescribed anatomical site of a compacted Gdf5-expressing mesenchymal interzone flanked by cartilaginous skeletal primordia. We and others previously showed that the interzone cells serve as progenitors and generate most joint tissues over time, including articular cartilage and ligaments. But how is the cavity formed within the compacted interzone? Because water accrual would be needed to create and inflate the cavity and in turn distance the flanking skeletal elements, cavity formation may require energy-consuming osmoregulatory mechanisms able to draw water and exert mechanical force. Our data now reveal that interzone cells in cavitating knee and digit mouse embryo joints strongly express the Na/K-ATPase pumps Atp1a1, Atp1b1 and Atp1b3, members of a key cell surface osmoregulatory protein family that regulates fluid tonicity and drawing of water. There was also local and specific expression of the water channel Aquaporin 1 (Aqp1). Single cell RNA seq (scRNAseq) showed that Gdf5+ interzone cells expressing those genes culminated in number at cavitation and were characterized by other osmoregulatory and mechano-sensing genes also. Indeed, when pregnant mice were administered ouabain -a physiological glycoside that normally limits Na/K-ATPase pump activity and osmoregulatory processes-, limb joint cavitation in the embryos was inhibited as was lubricant gene expression. Joint development is known to depend on signals from Indian hedgehog-expressing growth plate chondrocytes in flanking skeletal primordia. Interference with hedgehog signaling did coordinately inhibit expression of pump, mechano-sensing and lubricant genes as well as cavitation. Together, our data suggest a novel understanding of joint cavitation as an active energy-requiring osmoregulatory process able to accrue a water-based fluid, distance the flanking articulating surfaces and establish a synovial cavity in close coordination with long bone development and growth.
2025-07-29 | GSE276551 | GEO
Project description:In primates the amnion emerges through cavitation of the epiblast during implantation, whereas in other species by folding of the ectoderm later around gastrulation. How the mechanisms of amniogenesis diversified in evolution remains unknown. Here we employed the naïve-to-primed transition of human pluripotent stem cells (hPSC) to model peri-implantation epiblast development. We discovered that during this transition hPSC transiently gain the ability to differentiate into cavitating epithelium that transcriptionally matches the early amnion of human embryos. In contrast, primed hPSC produce cells resembling late amnion, uncovering an independent differentiation route. Unexpectedly, single-cell analysis of primate embryos revealed two transcriptionally distinct amniogenesis waves. The early wave occurs through a trophectoderm-like route and encompasses cavitation, whereas the late wave follows an ectoderm-like pathway during gastrulation. The discovery of two independent waves of amniogenesis both of which can be modelled in hPSC explains how amniogenesis through cavitation emerged during the evolution of primates.
2022-04-20 | GSE179309 | GEO
Project description:Cavitation in tuberculosis (TB) enables highly efficient person-to-person aerosol transmission. Currently, a number of hypotheses exist regarding the mechanisms underlying this process. To explore this process, we undertook an unbiased next-generation transcriptional analysis of samples from cavity walls, grossly normal tissue from the same lung, and uninfected control lungs. Of 17,318 mapped host transcripts, only 199 showed a significant >2-fold change in cavity wall versus normal infected and uninfected samples. Amongst 22 upregulated proteases, 5 type I collagenases were over-represented; these included cathepsin K (CTSK), mast cell chymase-1 (CMA1), matrix metalloproteinase (MMP)-1, MMP-13, and MMP-14. To determine if cavitation was associated with changes in collagen turnover, we assayed serum and urinary markers of collagen metabolism in rabbits with cavitary TB versus infected controls. Serum collagen type 1 C-terminal propeptide (CICP, a marker of collagen synthesis and degradation) and urinary deoxypyridinoline (DPD, a marker of degradation) were increased by 10- (p = 0.019) and 4-fold (p = 0.068), respectively; while urinary helical peptide (a marker of degradation) was decreased 3-fold (p=0.015). This indicates that cavitation in TB is associated with significant increases of both destruction and synthesis of collagen and that cleavage of type I collagen occurs outside the known cleavage sites of MMP-1, -13 and -14. Rabbit gene expression analysis in lung tissue from M. tuberculosis infected animals. Cavitary tissue, non cavitary tissue and lung tissue from non-infected animals are compared.
2015-11-03 | E-GEOD-68206 | biostudies-arrayexpress
Project description:During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development, still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z and independent of Zelda. H2A.Z enrichment precedes ZGA and Polymerase II loading onto chromatin. In vivo knock-down of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that maternal factors and H2A.Z are master regulators of the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
2021-10-13 | GSE161588 | GEO
Project description:During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development, still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z and independent of Zelda. H2A.Z enrichment precedes ZGA and Polymerase II loading onto chromatin. In vivo knock-down of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that maternal factors and H2A.Z are master regulators of the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
2021-10-13 | GSE173240 | GEO
Project description:During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development, still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z and independent of Zelda. H2A.Z enrichment precedes ZGA and Polymerase II loading onto chromatin. In vivo knock-down of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that maternal factors and H2A.Z are master regulators of the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
2021-10-13 | GSE161592 | GEO
Project description:During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development, still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z and independent of Zelda. H2A.Z enrichment precedes ZGA and Polymerase II loading onto chromatin. In vivo knock-down of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that maternal factors and H2A.Z are master regulators of the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
2021-10-13 | GSE161587 | GEO