Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence.
Changes in the Transcriptome of Human Astrocytes Accompanying Oxidative Stress-Induced Senescence.
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DOI：
10.3389/fnagi.2016.00208
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发表时间：
2016
影响因子：
4.8
通讯作者：
Torres C
中科院分区：
文献类型：
--
作者：
Crowe EP;Tuzer F;Gregory BD;Donahue G;Gosai SJ;Cohen J;Leung YY;Yetkin E;Nativio R;Wang LS;Sell C;Bonini NM;Berger SL;Johnson FB;Torres C
衰老对许多神经退行性疾病来说是一个主要风险因素。衰老生物学的一个关键特征可能是细胞衰老，这或许是这些疾病的潜在原因。随着年龄增长，衰老细胞在组织中累积，基因表达发生广泛变化，并且通常表现出改变的促炎特征。星形胶质细胞衰老与神经退行性疾病有关，为了更好地理解星形胶质细胞中与衰老相关的变化，我们利用RNA测序研究了其转录组的变化。通过短暂的氧化应激在人胎儿星形胶质细胞中诱导衰老。在衰老的星形胶质细胞中，包括那些参与神经元发育和分化的脑表达基因被下调。值得注意的是，几个表明星形胶质细胞对损伤反应的基因也被下调，包括胶质纤维酸性蛋白以及参与主要组织相容性复合体II类蛋白对抗原的加工和呈递的基因，而促炎基因被上调。总体而言，我们的研究结果表明，星形胶质细胞功能的衰老相关变化可能影响与年龄相关的脑部疾病的发病机制。
Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including glial fibrillary acidic protein and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.
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影响因子：
6.2
作者：
Chandley MJ;Crawford JD;Szebeni A;Szebeni K;Ordway GA
通讯作者：
Ordway GA
影响因子：
13.6
作者：
Freund A;Orjalo AV;Desprez PY;Campisi J
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Campisi J
影响因子：
64.8
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Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
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van Deursen JM
影响因子：
5.6
作者：
Barral S;Beltramo R;Salio C;Aimar P;Lossi L;Merighi A
通讯作者：
Merighi A
影响因子：
3.7
作者：
Elliott R;Li F;Dragomir I;Chua MM;Gregory BD;Weiss SR
通讯作者：
Weiss SR