Publications by authors named "Thorsten E Boroviak"

Article Synopsis
  • - The study investigates early human trophoblast development using marmoset embryos, bridging gaps in understanding due to the inaccessibility of human early conceptus.
  • - Researchers successfully created trophoblast stem cells (TSCs) from marmoset pluripotent stem cells, demonstrating unique characteristics and differentiation potential compared to human TSCs.
  • - The findings suggest that specific culture conditions for marmosets can maintain a trophoblast-like identity, revealing insights into evolutionary differences in implantation and enhancing knowledge of human development.
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The sperm epigenome is thought to affect the developmental programming of the resulting embryo, influencing health and disease in later life. Age-related methylation changes in the sperm of old fathers may mediate the increased risks for reproductive and offspring medical problems. The impact of paternal age on sperm methylation has been extensively studied in humans and, to a lesser extent, in rodents and cattle.

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Article Synopsis
  • Biomechanical cues are crucial for embryonic development and cell differentiation, and studying these can reveal how physical stimuli influence gene expression during early mammalian development.
  • By using microfluidic techniques to encapsulate mouse embryonic stem cells, researchers found that Plakoglobin (Jup), a key protein, enhances the network responsible for maintaining naive pluripotency.
  • The study highlights Plakoglobin's role as a mechanosensitive regulator, suggesting that its expression during blastocyst formation in both human and mouse embryos is vital for understanding cell fate transitions influenced by the physical environment.
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Human germline-soma segregation occurs during weeks 2-3 in gastrulating embryos. Although direct studies are hindered, here, we investigate the dynamics of human primordial germ cell (PGCs) specification using in vitro models with temporally resolved single-cell transcriptomics and in-depth characterisation using in vivo datasets from human and nonhuman primates, including a 3D marmoset reference atlas. We elucidate the molecular signature for the transient gain of competence for germ cell fate during peri-implantation epiblast development.

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Implantation of the conceptus into the uterus is absolutely essential for successful embryo development. In humans, our understanding of this process has remained rudimentary owing to the inaccessibility of early implantation stages. Non-human primates recapitulate many aspects of human embryo development and provide crucial insights into trophoblast development, uterine receptivity and embryo invasion.

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Article Synopsis
  • Primate embryogenesis is characterized by the early development of extraembryonic membranes, which is regulated by specific signals that influence cell lineages while protecting the pluripotent epiblast.
  • Researchers created a microgel system to culture marmoset pluripotent stem cells, successfully producing epiblast- and amnion-spheroids and verifying their identities against marmoset embryos.
  • Through single-cell analysis, they discovered that activin/nodal signaling is crucial for lineage identity, while BMP4 supports amnion development, with FGF signaling acting as an inhibitor, showcasing a new approach to studying early primate development.
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The trophoblast lineage safeguards fetal development by mediating embryo implantation, immune tolerance, nutritional supply and gas exchange. Human trophoblast stem cells (hTSCs) provide a platform to study lineage specification of placental tissues; however, the regulatory network controlling self-renewal remains elusive. Here, we present a single-cell atlas of human trophoblast development from zygote to mid-gestation together with single-cell profiling of hTSCs.

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Mammalian embryogenesis relies on glycolysis and oxidative phosphorylation to balance the generation of biomass with energy production. However, the dynamics of metabolic regulation in the postimplantation embryo in vivo have remained elusive due to the inaccessibility of the implanted conceptus for biochemical studies. To address this issue, we compiled single-cell embryo profiling data in six mammalian species and determined their metabolic dynamics through glycolysis and oxidative phosphorylation associated gene expression.

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Article Synopsis
  • Gastrulation is crucial for the development of cellular diversity and establishing bodily axes in early embryos, primarily driven by signaling centers in mammals.
  • This study explores the early gastrulation stages of marmoset embryos using advanced techniques like spatial transcriptomics and stem-cell models, revealing key molecular players involved in anterior visceral endoderm formation and primitive streak development.
  • The findings show that primate pluripotent stem cells (PSCs) closely resemble the anterior embryonic disc, providing insights into lineage specification and a reference for understanding human development.
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In this issue of Cell Stem Cell, Simunovic et al. (2022) establish embryoids by combining embryonic and extraembryonic components derived from human pluripotent stem cells. The embryoids resemble human embryos cultured to post-implantation stages in vitro with regard to morphology, symmetry breaking, and the formation of primitive streak-like cell types.

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Article Synopsis
  • The uterus is crucial for embryo implantation and fetal growth, but most current research focuses on later pregnancy stages to improve outcomes for premature births.
  • There is a need for in vitro (lab-based) models that concentrate on uterine tissue to better understand diseases like endometriosis and uterine cancers, as well as the process of embryo implantation.
  • The text suggests the possibility of creating stem cell-based models of the uterus using techniques like microfluidics and 3D printing to explore these important issues.
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Article Synopsis
  • Human periimplantation development involves transforming naive pluripotent epiblasts into a polarized epithelium, crucial for forming the amniotic cavity through lumenogenesis.
  • Researchers developed a high-throughput in vitro model using microfluidic technology to encapsulate human pluripotent stem cells (hPSCs) in microgels, leading to self-organizing polarized epiblast spheroids.
  • The study found that encapsulated primed hPSCs needed different conditions than naive hPSCs and showed increased lumen formation during the transition, providing a basis for future research on human epiblast development and organization.
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OCT4 is a fundamental component of the molecular circuitry governing pluripotency in vivo and in vitro. To determine how OCT4 establishes and protects the pluripotent lineage in the embryo, we used comparative single-cell transcriptomics and quantitative immunofluorescence on control and OCT4 null blastocyst inner cell masses at two developmental stages. Surprisingly, activation of most pluripotency-associated transcription factors in the early mouse embryo occurs independently of OCT4, with the exception of the JAK/STAT signaling machinery.

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Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by a secondary yolk sac during gastrulation. Moreover, primate embryos form extraembryonic mesoderm prior to gastrulation, in contrast to mouse.

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