Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation
Identification of astrocyte-expressed factors that modulate neural stem/progenitor cell differentiation
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DOI：
10.1089/scd.2006.15.407
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发表时间：
2006-06-01
影响因子：
4
通讯作者：
Zhao, Xinyu
中科院分区：
文献类型：
--
作者：
Barkho, Basam Z.;Song, Hongjun;Zhao, Xinyu
多能神经干/祖细胞（NSPCs）可以从成年中枢神经系统（CNS）的许多区域分离，但在体内神经发生仅限于海马和脑室下区。鉴定调节NSPC命运选择的分子线索是其治疗应用的先决条件。以前，我们证明，初级星形胶质细胞分离的区域具有较高的神经可塑性，如新生儿和成人海马和新生儿脊髓，促进成人NSPCs的神经元分化，而星形胶质细胞分离的非神经源性区域的成人脊髓抑制神经分化。为了确定这些星形胶质细胞表达的因素，可以调节NSPC分化，我们进行了基因表达谱分析使用Affyphyrin大鼠基因组阵列。我们的结果表明，这些星形胶质细胞有不同的基因表达谱。我们进一步测试了候选因子的功能作用，这些因子在体外NSPC分化试验中在促进神经发生和抑制神经发生的星形胶质细胞中差异表达。我们的研究结果表明，两种白细胞介素，IL-1 β和IL-6，以及包括这两种白细胞介素的因子的组合可以促进NSPC神经元分化，而胰岛素样生长因子结合蛋白6（IGFBP 6）和核心蛋白聚糖抑制成人NSPCs的神经元分化。我们的研究结果提供了进一步的证据来支持正在进行的假设，即在成年哺乳动物的大脑中，星形胶质细胞在调节NSPC分化中起着关键作用。星形胶质细胞表达的细胞因子和趋化因子可以促进NSPC神经元分化，这一发现可能有助于我们了解损伤如何诱导成人脑中的神经发生。
Multipotent neural stem/progenitor cells (NSPCs) can be isolated from many regions of the adult central nervous system (CNS), yet neurogenesis is restricted to the hippocampus and subventricular zone in vivo. Identification of the molecular cues that modulate NSPC fate choice is a prerequisite for their therapeutic applications. Previously, we demonstrated that primary astrocytes isolated from regions with higher neuroplasticity, such as newborn and adult hippocampus and newborn spinal cord, promoted neuronal differentiation of adult NSPCs, whereas astrocytes isolated from the nonneurogenic region of the adult spinal cord inhibited neural differentiation. To identify the factors expressed by these astrocytes that could modulate NSPC differentiation, we performed gene expression profiling analysis using Affymetrix rat genome arrays. Our results demonstrated that these astrocytes had distinct gene expression profiles. We further tested the functional effects of candidate factors that were differentially expressed in neurogenesis-promoting and -inhibiting astrocytes using in vitro NSPC differentiation assays. Our results indicated that two interleukins, IL-1 beta and IL-6, and a combination of factors that included these two interleukins could promote NSPC neuronal differentiation, whereas insulin-like growth factor binding protein 6 (IGFBP6) and decorin inhibited neuronal differentiation of adult NSPCs. Our results have provided further evidence to support the ongoing hypothesis that, in adult mammalian brains, astrocytes play critical roles in modulating NSPC differentiation. The finding that cytokines and chemokines expressed by astrocytes could promote NSPC neuronal differentiation may help us to understand how injuries induce neurogenesis in adult brains.