Martin Leeb is a Group Leader at Max Perutz Labs in Vienna. His research focuses on the molecular mechanisms controlling pluripotency and cell fate decisions during early embryonic development, particularly around the time of implantation.
Pluripotency enables stem cells to generate any embryonic cell type, a capacity controlled by intricate gene regulatory networks. A key milestone in early development is the transition from the naïve to the formative state of pluripotency, which parallels embryo implantation. This shift endows the epiblast with the potential to initiate germ layer differentiation and germline specification, a decisive step in embryogenesis. Understanding the molecular logic of this transition is critical for closing fundamental gaps in our knowledge of mammalian development. To address this, we apply integrated, high-resolution systems biology approaches combined with CRISPR-based genetic screens to identify key drivers of naïve exit and formative state establishment. This revealed several previously unrecognized factors that promote formative pluripotency, including isoform-specific regulators. Comparative analyses between human and mouse uncovered striking species-specific differences in regulon activity and cell fate control. Many pathways well-characterized in mouse are inactive or functionally divergent in the human context. These findings expose fundamental species-specific mechanisms governing the maintenance and dissolution of pluripotency.
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