Sato Yuya, Uchida Yutaka, Hu Jingqiong, Young-Pearse Tracy L, Niikura Takako, Mukouyama Yoh-Suke
Laboratory of Stem Cell and Neuro-Vascular Biology, Genetics and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10/6C103, 10 Center Drive, Bethesda, MD 20892, USA.
Stem Cell Center, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.
Development. 2017 Aug 1;144(15):2730-2736. doi: 10.1242/dev.143370. Epub 2017 Jul 10.
The molecular mechanism by which NSC number is controlled in the neurogenic regions of the adult brain is not fully understood but it has been shown that vascular niche signals regulate neural stem cell (NSC) quiescence and growth. Here, we have uncovered a role for soluble amyloid precursor protein (sAPP) as a vascular niche signal in the subventricular zone (SVZ) of the lateral ventricle of the adult mouse brain. sAPP suppresses NSC growth in culture. Further studies on the role of APP in regulating NSC number in the SVZ clearly demonstrate that endothelial deletion of causes a significant increase in the number of BrdU label-retaining NSCs in the SVZ, whereas NSC/astrocyte deletion of has no detectable effect on the NSC number. Taken together, these results suggest that endothelial APP functions as a vascular niche signal that negatively regulates NSC growth to control the NSC number in the SVZ.
成人大脑神经发生区域中神经干细胞（NSC）数量的调控分子机制尚未完全明确，但已有研究表明，血管微环境信号可调节神经干细胞的静止和生长。在此，我们发现可溶性淀粉样前体蛋白（sAPP）在成年小鼠脑侧脑室室管膜下区（SVZ）作为一种血管微环境信号发挥作用。sAPP在培养中可抑制神经干细胞生长。对APP在调控SVZ神经干细胞数量方面作用的进一步研究清楚地表明，在内皮细胞中敲除APP会导致SVZ中BrdU标记保留神经干细胞的数量显著增加，而在神经干细胞/星形胶质细胞中敲除APP对神经干细胞数量没有可检测到的影响。综上所述，这些结果表明内皮细胞中的APP作为一种血管微环境信号，通过负向调节神经干细胞生长来控制SVZ中的神经干细胞数量。
