A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain.
A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain.
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DOI：
10.1002/jnr.24082
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发表时间：
2018-03
影响因子：
4.2
通讯作者：
Iliff JJ
中科院分区：
文献类型：
--
作者：
Simon MJ;Murchison C;Iliff JJ
星形胶质细胞在调节脑血管系统和中枢神经系统之间的界面中起关键作用。星形胶质细胞端足结构域对此有贡献，这是一种包裹整个脉管系统并介导内皮细胞、周细胞和神经元之间的信号传导的专门结构。星形胶质细胞终足被认为是胶质淋巴通路的关键元件，并且该细胞域中蛋白质表达谱的变化与阿尔茨海默病病理学有关。尽管如此，这种结构的基本生理特性仍然知之甚少，包括其形成的发育时间，以及定位在那里以介导其功能的蛋白质组分。在这里，我们使用人类转录组数据，从男性和女性受试者在几个发展阶段和大脑区域的肌营养不良蛋白相关复合物（DAC），一个已知的结构组成部分，支持血管周围定位的星形胶质细胞水通道水通道蛋白-4（AQP4）的星形胶质细胞endfoot的基因表达谱的特征。转录组学分析也用于定义表现出与DAC元件平行的表达谱的基因，产生编码可能有助于血管周围星形胶质细胞端足结构域的生理功能的基因产物的候选基因库。我们发现几个编码转运蛋白的基因在转录上与DAC基因相关。星形胶质细胞终足是神经血管单位的重要组成部分，但其发育时间和蛋白质成分的定义很差。一种已建立的组分是肌营养不良蛋白相关复合物（DAC）。在这里，开发人脑转录组数据被用来表征DAC基因的时间表达和识别转录相关基因。
Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway and changes in protein expression profiles in this cellular domain are linked to Alzheimer’s disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4 (AQP4). Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes. The astrocytic endfoot is a critical component of the neurovascular unit, yet its developmental timing and protein constituents are poorly defined. One established component is the dystrophin associated complex (DAC). Here, developing human brain transcriptome data is used to characterize temporal expression of DAC genes and identify transcriptionally linked genes.
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影响因子：
11.8
作者：
Chau KF;Springel MW;Broadbelt KG;Park HY;Topal S;Lun MP;Mullan H;Maynard T;Steen H;LaMantia AS;Lehtinen MK
通讯作者：
Lehtinen MK
影响因子：
5.3
作者：
Boulay AC;Saubaméa B;Cisternino S;Mignon V;Mazeraud A;Jourdren L;Blugeon C;Cohen-Salmon M
通讯作者：
Cohen-Salmon M
影响因子：
12.7
作者：
Boor, Ilja;Nagtegaal, Machiel;Kamphorst, Wouter;van der Valk, Paul;Pronk, Jan C.;van Horssen, Jack;Dinopoulos, Argirios;Bove, Kevin E.;Pascual-Castroviejo, Ignacio;Muntoni, Francesco;Estevez, Raul;Scheper, Gert C.;van der Knaap, Marjo S.
通讯作者：
van der Knaap, Marjo S.
影响因子：
1.9
作者：
Gato A;Alonso MI;Martín C;Carnicero E;Moro JA;De la Mano A;Fernández JM;Lamus F;Desmond ME
通讯作者：
Desmond ME
影响因子：
5.6
作者：
Hiroaki, Y;Tani, K;Fujiyoshi, Y
通讯作者：
Fujiyoshi, Y