Beyond the blastocyst: modeling human embryology with stem cells
Chromosomal aneuploidies are frequently found in human IVF embryos and are a main cause of pregnancy loss. Progress in the study of human development and the impact of aneuploidies is slow due to the limited number of embryos available for research and experimental and ethical constraints. Here, we will use newly developed human blastoids, models of the blastocyst-stage embryo generated entirely from stem cells, to analyse the mechanisms of human development at an unprecedented level of cellular and molecular detail. Our multidisciplinary consortium will combine advanced single-cell (epi-)genomic and proteomic technologies, phosphoproteomics, real-time imaging and microfluidics to construct a 4D map of human development and dissect the cellular interactions that guide early cell-fate decisions and morphogenesis. We will then investigate how chromosomal aberrations affect these developmental mechanisms and explore interventions that promote healthy development. In complementary research, we will develop an ethical framework for sound policy-making with regards to human embryo model research and its clinical applications.
Our project on the molecular dissection of human embryonic development will directly impact our understanding of human embryology and the genesis of birth defects. Moreover, it will improve in vitro reproductive technologies and support clinical decision-making in response to detection of aneuploidies.
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Derk ten Berge
Role Erasmus MC: