Institut National de la Santé et de la Recherche Médicale (INSERM) U583, Physiopathologie et Thérapie des déficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, Hôpital St. ELOI, Montpellier, France.
Stem Cells. 2009 Nov;27(11):2722-33. doi: 10.1002/stem.226.
In humans and rodents the adult spinal cord harbors neural stem cells located around the central canal. Their identity, precise location, and specific signaling are still ill-defined and controversial. We report here on a detailed analysis of this niche. Using microdissection and glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP) transgenic mice, we demonstrate that neural stem cells are mostly dorsally located GFAP(+) cells lying ependymally and subependymally that extend radial processes toward the pial surface. The niche also harbors doublecortin protein (Dcx)(+) Nkx6.1(+) neurons sending processes into the lumen. Cervical and lumbar spinal cord neural stem cells maintain expression of specific rostro-caudal Hox gene combinations and the niche shows high levels of signaling proteins (CD15, Jagged1, Hes1, differential screening-selected gene aberrative in neuroblastoma [DAN]). More surprisingly, the niche displays mesenchymal traits such as expression of epithelial-mesenchymal-transition zinc finger E-box-binding protein 1 (ZEB1) transcription factor and smooth muscle actin. We found ZEB1 to be essential for neural stem cell survival in vitro. Proliferation within the niche progressively ceases around 13 weeks when the spinal cord reaches its final size, suggesting an active role in postnatal development. In addition to hippocampus and subventricular zone niches, adult spinal cord constitutes a third central nervous system stem cell niche with specific signaling, cellular, and structural characteristics that could possibly be manipulated to alleviate spinal cord traumatic and degenerative diseases.
在人类和啮齿动物中，成年脊髓内含有位于中央管周围的神经干细胞。它们的身份、确切位置和特定信号仍然定义不明确，存在争议。我们在此报告对这一生态位的详细分析。我们利用显微解剖和胶质纤维酸性蛋白（GFAP）-绿色荧光蛋白（GFP）转基因小鼠，证明神经干细胞主要是位于背侧的 GFAP(+)细胞，位于室管膜和室下膜，向软脑膜表面伸出放射状突起。该生态位还包含双皮质蛋白（Dcx）（+) Nkx6.1(+)神经元，其突起进入管腔。颈段和腰段脊髓神经干细胞维持特定的前后轴 Hox 基因组合的表达，并且该生态位显示高水平的信号蛋白（CD15、Jagged1、Hes1、神经母细胞瘤差异筛选选择基因异常[DAN]）。更令人惊讶的是，该生态位显示出间充质特征，如上皮-间充质转化锌指 E 盒结合蛋白 1（ZEB1）转录因子和平滑肌肌动蛋白的表达。我们发现 ZEB1 对于体外神经干细胞的存活是必需的。当脊髓达到最终大小时，生态位内的增殖在 13 周左右逐渐停止，这表明其在出生后发育中具有积极作用。除了海马和侧脑室下区生态位外，成年脊髓构成了第三个中枢神经系统干细胞生态位，具有特定的信号、细胞和结构特征，可能被操纵以缓解脊髓创伤和退行性疾病。
