成年室管膜下区神经干细胞在中风后可分化为皮质反应性星形胶质细胞。

Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke.

机构信息

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3H7, Canada.

Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada.

出版信息

Cell Stem Cell. 2015 Nov 5;17(5):624-34. doi: 10.1016/j.stem.2015.08.002. Epub 2015 Oct 8.

Abstract

Reactive astrocytes (RAs) have been reported to convert to multipotent neural stem cells (NSCs) capable of neurosphere (NS) formation and multilineage differentiation in vitro. Using genetic tagging, we determined that subventricular zone (SVZ) NSCs give rise to NSs derived from the stroke-injured cortex. We demonstrate that these cells can be isolated from the cortex in two different models of stroke and from different stroke-lesioned cortical regions. Interestingly, SVZ NSCs give rise to a subpopulation of RAs in the cortex that contribute to astrogliosis and scar formation. Last, we show that these SVZ derived RAs can be converted to neurons in vivo by forced expression of Ascl1. Identifying the contribution of cells originating from the SVZ to injury repair has implications for neural regeneration strategies.

摘要

反应性星形胶质细胞(RAs)已被报道可转化为多能神经干细胞(NSCs),这些细胞在体外具有形成神经球(NS)和多谱系分化的能力。通过遗传标记,我们确定侧脑室下区(SVZ)NSCs 产生源自脑损伤皮层的 NS。我们证明,这些细胞可以从两种不同的中风模型和不同的中风损伤皮层区域中从皮层中分离出来。有趣的是,SVZ NSCs 产生了皮层中反应性星形胶质细胞的一个亚群,这些细胞有助于星形胶质细胞增生和疤痕形成。最后,我们表明,通过强制表达 Ascl1,这些源自 SVZ 的反应性星形胶质细胞可以在体内转化为神经元。确定源自 SVZ 的细胞对损伤修复的贡献,对神经再生策略具有重要意义。

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