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Nat Commun ; 4: 2049, 2013.
Article in English | MEDLINE | ID: mdl-23804023

ABSTRACT

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 α-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 α-tanycytes are self-renewing cells that constitutively give rise to new tanycytes, astrocytes and sparse numbers of neurons. In vitro studies demonstrate that α-tanycytes, but not ß-tanycytes or parenchymal cells, are neurospherogenic. Distinct subpopulations of α-tanycytes exist, amongst which only GFAP-positive dorsal α2-tanycytes possess stem-like neurospherogenic activity. Fgf-10 and Fgf-18 are expressed specifically within ventral tanycyte subpopulations; α-tanycytes require fibroblast growth factor signalling to maintain their proliferation ex vivo and elevated fibroblast growth factor levels lead to enhanced proliferation of α-tanycytes in vivo. Our results suggest that α-tanycytes form the critical component of a hypothalamic stem cell niche, and that local fibroblast growth factor signalling governs their proliferation.


Subject(s)
Aging/metabolism , Ependymoglial Cells/metabolism , Fibroblast Growth Factor 10/metabolism , Fibroblast Growth Factors/metabolism , Hypothalamus/cytology , Neural Stem Cells/metabolism , Third Ventricle/cytology , Animals , Cell Proliferation/drug effects , Ependymoglial Cells/cytology , Ependymoglial Cells/drug effects , Epidermal Growth Factor/pharmacology , Excitatory Amino Acid Transporter 1/metabolism , Glial Fibrillary Acidic Protein/metabolism , Immunohistochemistry , Integrases/metabolism , Mice , Mice, Inbred C57BL , Neural Stem Cells/cytology , Neural Stem Cells/drug effects , Neuroglia/cytology , Neuroglia/drug effects , Neuroglia/metabolism , Signal Transduction/drug effects , Spheroids, Cellular/cytology , Spheroids, Cellular/drug effects , Spheroids, Cellular/metabolism
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