Project description:Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo.
Project description:Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo.
Project description:Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo.
Project description:Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo.
Project description:Gastrulation and early organogenesis are remarkable processes of early embryonic development. Our previous study showed that deletion of DYT6 gene product THAP1 leads to embryonic lethality at the stage of gastrulation and early organogenesis. However, the function of THAP1 in regulating gene expression, as well as its role in regulating embryo gastrulation and early organogenesis are not well characterized. In this study, we used different in vitro and in vivo models to characterize the function of THAP1 in regulating gene expression and in controlling embryonic development, which could help us to understand pathogenesis of THAP1-associated disorders and provide data to characterize the transcription regulation of gastrulation of murine embryo.
Project description:Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, non-human primates (NHPs) are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we have collected six Carnegie stage (CS) 8-CS11 cynomolgus monkey embryos and performed in-depth transcriptome analyses of 56,636 single cells. Our analyses reveal transcriptomic features of major peri-gastrulation cell types, which help shed light on morphogenetic events including primitive streak (PS) development, somitogenesis, gut tube formation, neural tube patterning, and neural crest regionalization in primates. In addition, comparative analyses with mouse embryos and human embryoids uncover conserved and divergent features of peri-gastrulation development across species, e.g. species-specific dependency on Hippo signaling during presomitic mesoderm differentiation, and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the NHP research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders.
Project description:We characterised the transcriptomic profiles of 146,133 individual cells (post-QC) from whole rabbit embryos spanning gestational days 7, 8 and 9. These experiments were performed to elucidate the molecular programmes underlying gastrulation and early organogenesis in a non-rodent mammal. Combined with existing datasets of early mouse development, our rabbit developmental atlas facilitates a broad cross-species approach to deciphering early human development. Cell libraries were prepared using the 10X Genomics Chromium platform.
Project description:Gastrulation is the highly coordinated process by which the early embryo breaks symmetry, establishes germ layers and a body plan, and sets the stage for organogenesis. As early mammalian development is challenging to study in vivo, stem cell-derived models have emerged as powerful surrogates, e.g. human and mouse gastruloids. However, although single cell RNA-seq (scRNA-seq) and high-resolution imaging have been extensively applied to characterize such in vitro embryo models, a paucity of measurements of protein dynamics and regulation leaves a major gap in our understanding. Here we sought to address this by applying quantitative proteomics to human and mouse gastruloids at four key stages of their differentiation (naïve ESCs, primed ESCs, early gastruloids, late gastruloids). To the resulting data, we perform network analysis to map the dynamics of expression of macromolecular protein complexes and biochemical pathways, including identifying cooperative proteins that associate with them. With matched RNA-seq and phosphosite data from these same stages, we investigate pathway-, stage- and species-specific aspects of translational and post-translational regulation, e.g. finding peri-gastrulation stages of human vs. mice to be discordant with respect to the mitochondrial transcriptome vs. proteome, and nominating novel kinase-substrate relationships based on phosphosite dynamics. Finally, we leverage correlated dynamics to identify conserved protein networks centered around congenital disease genes. Altogether, our study showcases the potential of intersecting proteomics and in vitro embryo models to advance our understanding of early mammalian development in ways that may not be possible through transcriptomics alone.
Project description:Studies in mouse have led to enormous progress in our understanding of early human development. The identification of genes and the signaling pathways involved in mouse embryogenesis have helped us to better understand fertilization, morulation, gastrulation, organogenesis and embryonic development in mammals. We report a detailed analysis of the global gene expression profiles from oocyte to the end of organogenesis in mouse. Our studies revealed distinct temporal regulation patterns for genes belonging to different functional categories, supporting their roles during organogenesis.