Assistant Professor Westlake University Hangzhou, Zhejiang, China (People's Republic)
Abstract: Human peri-gastrulation development remains poorly understood, primarily due to limited access to in vivo embryos and ethical constraints. Stem-cell-derived embryo models, such as peri-gastruloids, offer unique opportunities to investigate this critical stage of human development. However, their ability to mimic in vivo development requires further exploration. Here, we present a comprehensive, time-resolved analysis of human peri-gastruloids, integrating single-cell RNA-seq, single-nucleus ATAC-seq, and metabolomics across key stages. We show that human peri-gastruloids recapitulate peri-gastrulation development, from bilaminar to trilaminar disc formation and early organogenesis, at both cellular and molecular levels. Time-resolved transcriptional and chromatin accessibility profiling reveals critical lineage regulators, shedding light on transcription factors driving lineage specification and maintenance. Metabolomic profiling further identifies stage-specific metabolic signatures, while integration with gene expression data uncovers coordinated metabolic and transcriptional regulation during human peri-gastruloid development. Importantly, we demonstrate the utility of peri-gastruloids for teratogenicity test, showing that Methotrexate disrupts critical metabolic pathways such as cholesterol homeostasis and neural ectoderm formation, mirroring clinical observations of its teratogenic effects. Together, these findings establish peri-gastruloids as a robust model for studying human development, with potential applications in disease modeling and drug safety assessment.
Funding Source: New York Stem Cell Foundation (NYSCF); American Society for Reproductive Medicine (ASRM)
