Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation.
Microarray analyses reveal regional astrocyte heterogeneity with implications for neurofibromatosis type 1 (NF1)-regulated glial proliferation.
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DOI：
10.1002/glia.20845
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发表时间：
2009-08-15
期刊：
影响因子：
6.2
通讯作者：
Gutmann, David H.
中科院分区：
文献类型：
--
作者：
Yeh, Tu-Hsueh;Lee, Da Yong;Gianino, Scott M.;Gutmann, David H.
大量研究表明中枢神经系统（CNS）中的星形胶质细胞表现出分子和功能异质性。在这方面，来自不同中枢神经系统位置的星形胶质细胞表达不同的免疫系统和神经递质蛋白，具有不同水平的间隙连接耦合，并且对损伤的反应不同。然而，这些差异与人类疾病的相关性尚不清楚。由于儿童脑肿瘤发生在特定的中枢神经系统位置，我们假设区域星形胶质细胞异质性可能部分是这些区域发生神经胶质瘤的倾向的基础。在这项研究中，我们对出生后第 1 天视神经、小脑、脑干和新皮质的星形胶质细胞进行了高密度 RNA 微阵列分析。我们发现来自每个区域的星形胶质细胞在分子上是不同的，并且我们能够开发出基因表达模式来区分来自这些不同大脑区域的星形胶质细胞，但不能区分神经干细胞。接下来，我们使用这些微阵列数据来确定脑肿瘤抑制基因在这些不同的星形胶质细胞群体中是否存在差异表达。有趣的是，与其他大脑区域的星形胶质细胞相比，新皮质星形胶质细胞的 1 型神经纤维瘤病 (NF1) 基因表达在 RNA 和蛋白质水平上均降低。为了确定这一发现的功能意义，我们发现在体外和体内 Nf1 失活后，视神经、脑干和小脑中的星形胶质细胞增殖增加，但新皮质则没有增加。这些发现为中枢神经系统星形胶质细胞异质性提供了分子证据，并表明肿瘤抑制基因表达的差异可能有助于人脑肿瘤的区域定位。
Numerous studies have suggested that astrocytes in the central nervous system (CNS) exhibit molecular and functional heterogeneity. In this regard, astrocytes from different CNS locations express distinct immune system and neurotransmitter proteins, have varying levels of gap junction coupling, and respond differently to injury. However, the relevance of these differences to human disease is unclear. Since brain tumors in children arise in specific CNS locations, we hypothesized that regional astrocyte heterogeneity might partly underlie the propensity for gliomas to arise in these areas. In this study, we performed high-density RNA microarray profiling on astrocytes from postnatal day 1 optic nerve, cerebellum, brainstem, and neocortex. We showed that astrocytes from each region are molecularly distinct, and we were able to develop gene expression patterns that distinguish astrocytes, but not neural stem cells, from these different brain regions. We next used these microarray data to determine whether brain tumor suppressor genes were differentially expressed in these distinct populations of astrocytes. Interestingly, neurofibromatosis type 1 (NF1) gene expression was decreased at both the RNA and protein levels in neocortical astrocytes relative to astrocytes from the other brain regions. To determine the functional significance of this finding, we found increased astrocyte proliferation in optic nerve, brainstem, and cerebellum, but not neocortex, following Nf1 inactivation in vitro and in vivo. These findings provide molecular evidence for CNS astrocyte heterogeneity, and suggest that differences in tumor suppressor gene expression might contribute to the regional localization of human brain tumors.
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DOI：
10.1016/0169-328x(91)90022-p
发表时间：
1991-08-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
BATTER, DK;KESSLER, JA
通讯作者：
KESSLER, JA
影响因子：
2.9
作者：
KLEIN, RS;FRICKER, LD
通讯作者：
FRICKER, LD
影响因子：
--
作者：
RODRIGUEZ, HA;BERTHRONG, M
通讯作者：
BERTHRONG, M
影响因子：
11.2
作者：
Hegedus, Balazs;Banerjee, Debasish;Gutmann, David H.
通讯作者：
Gutmann, David H.
影响因子：
3.9
作者：
Butt, AM;Pugh, M;James, G
通讯作者：
James, G