成年下丘脑第三脑室的 α-室管膜细胞包括不同群体的 FGF 反应性神经前体细胞。

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

机构信息

MRC Centre for Developmental and Biomedical Genetics and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.

出版信息

Nat Commun. 2013;4:2049. doi: 10.1038/ncomms3049.

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 β-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.

摘要

新的证据表明,新的细胞,包括神经元,可以在成年下丘脑内产生,这表明存在局部神经干细胞/祖细胞龛。在这里,我们确定 α-桶状细胞是成年小鼠下丘脑龛中的关键组成部分。体内使用 GLAST::CreER(T2)条件性驱动进行的长期谱系追踪表明,α-桶状细胞是自我更新的细胞,它们持续产生新的桶状细胞、星形胶质细胞和少量神经元。体外研究表明,α-桶状细胞而非β-桶状细胞或实质细胞具有神经球生成能力。α-桶状细胞存在不同的亚群,其中只有 GFAP 阳性的背侧 α2-桶状细胞具有干细胞样的神经球生成活性。Fgf-10 和 Fgf-18 特异性表达于腹侧桶状细胞亚群内;α-桶状细胞需要成纤维细胞生长因子信号来维持其体外增殖,并且升高的成纤维细胞生长因子水平导致体内 α-桶状细胞增殖增强。我们的结果表明,α-桶状细胞形成了下丘脑干细胞龛的关键组成部分,并且局部成纤维细胞生长因子信号调节它们的增殖。

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