The Road from Pluripotency to Lineage Determination.

Every cell in your body began as a blank slate—a pluripotent cell with no fixed identity—and this project aims to catch those cells in the moment they first commit to becoming a specific tissue type. The research addresses a fundamental gap in developmental biology: how do naive, uncommitted cells exit their ground state and choose a lineage? Current evidence suggests that transcription factors, not epigenetic marks, govern pluripotency, but the transition from that state to lineage commitment remains poorly understood. The team hypothesises that fibroblast growth factor stimulation of the MAP kinase cascade destabilises the ground state, creating a metastable condition where cells are poised for multilineage commitment. They will isolate cells in this transition and analyse their regulatory circuitry using quantitative transcriptomics, proteomics, biochemistry, genetic manipulation, and live cell tracking. This is fundamental science with no immediate practical application. However, understanding the design principles of pluripotency and lineage choice could eventually improve the efficiency and safety of stem cell therapies, organoid generation, and regenerative medicine—fields that rely on coaxing stem cells into specific cell types. Similar fundamental work on pluripotency transcription factors led directly to induced pluripotent stem cell technology, which transformed biomedical research.