Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models.
Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models.
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DOI：
10.3389/fnmol.2022.870085
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发表时间：
2022
影响因子：
4.8
通讯作者：
Fossati, Valentina
中科院分区：
文献类型：
--
作者：
Labib, David;Wang, Zhen;Prakash, Priya;Zimmer, Matthew;Smith, Matthew D.;Frazel, Paul W.;Barbar, Lilianne;Sapar, Maria L.;Calabresi, Peter A.;Peng, Junmin;Liddelow, Shane A.;Fossati, Valentina
关键词：
星形胶质细胞对中枢神经系统中的损伤、感染和炎症作出反应，通过获得反应性状态，在该反应性状态下，星形胶质细胞可能变得功能障碍并促成疾病病理学。由促炎因子TNF、IL-1α和C1 q（“TIC”）诱导的反应性星形胶质细胞的亚状态已经作为神经毒性的来源涉及许多神经变性疾病。在这里，我们使用了一个建立的人诱导多能干细胞（hiPSC）模型，研究表面标记物的轮廓和蛋白质组的TIC诱导的反应性星形胶质细胞。我们提出VCAM 1，BST 2，ICOSL，HLA-E，PD-L1和PDPN作为这种反应性亚状态的推定的新标记物。我们发现这些标记物中的几个与阿尔茨海默病患者死后样本中的GFAP+细胞共定位。此外，我们对TIC诱导的反应性星形胶质细胞进行了全细胞蛋白质组学分析，确定了主要与外周免疫细胞潜在参与相关的蛋白质和相关途径。总之，我们的研究结果将作为纯化反应性星形胶质细胞亚型的新工具，并进一步探索它们参与与损伤和疾病相关的免疫反应。
Astrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q (“TIC”) has been implicated in many neurodegenerative diseases as a source of neurotoxicity. Here, we used an established human induced pluripotent stem cell (hiPSC) model to investigate the surface marker profile and proteome of TIC-induced reactive astrocytes. We propose VCAM1, BST2, ICOSL, HLA-E, PD-L1, and PDPN as putative, novel markers of this reactive sub-state. We found that several of these markers colocalize with GFAP+ cells in post-mortem samples from people with Alzheimer’s disease. Moreover, our whole-cells proteomic analysis of TIC-induced reactive astrocytes identified proteins and related pathways primarily linked to potential engagement with peripheral immune cells. Taken together, our findings will serve as new tools to purify reactive astrocyte subtypes and to further explore their involvement in immune responses associated with injury and disease.
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影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
7.3
作者：
Astarita JL;Acton SE;Turley SJ
通讯作者：
Turley SJ
影响因子：
5.9
作者：
Douvaras P;Sun B;Wang M;Kruglikov I;Lallos G;Zimmer M;Terrenoire C;Zhang B;Gandy S;Schadt E;Freytes DO;Noggle S;Fossati V
通讯作者：
Fossati V
影响因子：
16.2
作者：
Bai, Bing;Wang, Xusheng;Peng, Junmin
通讯作者：
Peng, Junmin
来自小鼠大脑多个区域的老化星形胶质细胞转录组。
影响因子：
8.8
作者：
Boisvert MM;Erikson GA;Shokhirev MN;Allen NJ
通讯作者：
Allen NJ