A5009062139- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Reproductive System and Pregnancy
- Single-cell and spatial transcriptomics
- Prenatal Screening and Diagnostics
- Mesenchymal stem cell research
- Renal and related cancers
- Autophagy in Disease and Therapy
- Cancer Genomics and Diagnostics
- Congenital heart defects research
- Cancer-related gene regulation
- Tissue Engineering and Regenerative Medicine
- Reproductive Biology and Fertility
University of Cambridge
2019-2024
California Institute of Technology
2024
Abstract The high incidence of aneuploidy in the embryo is considered principal cause for low human fecundity. However, prevalence dramatically declines as pregnancy progresses, with steepest drop occurring completes implantation. Despite fact that plasticity dealing fundamental to normal development, mechanisms responsible eliminating aneuploid cells are unclear. Here, using a mouse model chromosome mosaicism, we show preferentially eliminated from embryonic lineage p53-dependent process...
Abstract The human embryo undergoes morphogenetic transformations following implantation into the uterus, but our knowledge of this crucial stage is limited by inability to observe in vivo. Models derived from stem cells are important tools for interrogating developmental events and tissue–tissue crosstalk during these stages 1 . Here we establish a model post-implantation embryo, embryoid, comprising embryonic extraembryonic tissues. We combine two types extraembryonic-like cell generated...
Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to 2-cell stage embryo. However, whether and how such asymmetries arise embryo is unclear. Here, we performed prospective tracing human embryos using live imaging, non-invasive cell labeling, computational predictions determine contribution each blastomere epiblast (body), hypoblast (yolk sac), trophectoderm (placenta). We show majority cells originate from only one observe three...
Abstract Development requires coordinated interactions between the epiblast, which generates embryo proper; trophectoderm, placenta; and hypoblast, forms both anterior signalling centre yolk sac. These remain poorly understood in human embryogenesis because mechanistic studies have only recently become possible. Here we examine post-implantation using embryos stem cell models of epiblast hypoblast. We find hypoblast specification is NODAL dependent, as mouse. However, while BMP inhibits...
Abstract Protein Arginine (R) methylation is the most common post-translational in mammalian cells. Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically symmetrically, respectively. They are ubiquitously expressed play fundamental roles tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with GBM cells, modulating, at least part, its...
Abstract Pre-patterning of the embryo, driven by spatially localized factors, is a common feature across several non-mammalian species 1–4 . However, mammals display regulative development and thus it was thought that blastomeres embryo do not show such pre-patterning, contributing randomly to three lineages blastocyst: epiblast, primitive endoderm trophectoderm will generate new organism, yolk sac placenta respectively 4–6 Unexpectedly, early mouse human embryos have been reported distinct...
Abstract The human embryo undergoes morphogenetic transformations following implantation into the uterus, yet our knowledge of this crucial stage is limited by inability to observe in vivo . Stem cell-derived models are important tools interrogate developmental events and tissue-tissue crosstalk during these stages 1 Here, we establish a post-implantation model comprised embryonic extraembryonic tissues. We combine two types extraembryonic-like cells generated transcription factor...
Protein Arginine (R) methylation is the most common post-translational in mammalian cells. Methyltransferases (PRMT) 1 and 5 dimethylate their substrates on R residues, asymmetrically symmetrically, respectively. They are ubiquitously expressed play fundamental roles tumour malignancies, including glioblastoma multiforme (GBM) which presents largely deregulated Myc activity. Previously, we demonstrated that PRMT5 associates with GBM cells, modulating, at least part, its transcriptional...