Grant: Project Grant

The hypothalamus is the brain's control centre for hunger, thirst, sleep, body temperature, and memory-linked circuits. We have discovered a previously unrecognized neural stem cell in the posterior regions of the hypothalamus that we term tanycyte stem cells (TSCs). Unlike the traditional radial glial cells that are the precursors for neurons across most of the brain, TSCs appear in embryos, persist into adulthood, and both sense signals in the blood or cerebrospinal fluid and generate new neurons. Our data suggest that TSCs follow a direct program from neuroepithelial cell to TSC to neurons. In this proposal, we will determine when TSCs first appear, what neuronal cells they produce, and where they live using single-cell and spatial transcriptomics. Because TSCs sit at the fluid-brain interface, we will test whether a high-fat diet during pregnancy changes how many neurons they make and whether it leaves an "imprint" that alters how adult TSCs respond to diet later in life. By revealing this new stem cell program and its sensitivity to the prenatal environment, our work could shift therapies from acting on neurons to preserving and tuning the TSC niche, ultimately helping to prevent or reduce lifelong risks tied to early nutrition exposure.