α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors

Emerging evidence suggests that new cells, including neurons, can be generated within the adult hypothalamus, suggesting the existence of a local neural stem/progenitor cell niche. Here, we identify alpha-tanycytes as key components of a hypothalamic niche in the adult mouse. Long-term lineage tracing in vivo using a GLAST::CreER(T2) conditional driver indicates that alpha-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that alpha-tanycytes, but not beta-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of alpha-tanycytes exist, amongst which only GFAP-positive dorsal alpha 2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; alpha-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of alpha-tanycytes in vivo. Our results suggest that alpha-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation.