A shared disease-associated oligodendrocyte signature among multiple CNS pathologies.
A shared disease-associated oligodendrocyte signature among multiple CNS pathologies.
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在多种CNS病理中共享的疾病相关少突胶质细胞特征
DOI：
10.1038/s41593-022-01104-7
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发表时间：
2022-07
影响因子：
25
通讯作者：
Amit, Ido
中科院分区：
文献类型：
--
作者：
Kenigsbuch, Mor;Bost, Pierre;Halevi, Shahar;Chang, Yuzhou;Chen, Shuo;Ma, Qin;Hajbi, Renana;Schwikowski, Benno;Bodenmiller, Bernd;Fu, Hongjun;Schwartz, Michal;Amit, Ido
阿尔茨海默病（AD）是一种复杂的神经退行性疾病，扰乱神经元和非神经元细胞群。在这里，使用单细胞转录组学，我们绘制了野生型和AD模型（5xFAD）小鼠大脑中的所有非免疫、非神经元细胞群。我们发现了一种与脑病理相关的少突胶质细胞状态，我们称之为疾病相关的少突胶质细胞（DOLs）。在小鼠淀粉样变性模型中，DOL在斑块积累后很长时间才出现，仅淀粉样蛋白β (a β)不足以在体外诱导DOL特征。DOLs可以在牛头病小鼠模型和其他小鼠神经退行性疾病和自身免疫性炎症中发现，表明对严重病理条件的共同反应。通过对小鼠和死后人脑组织的定量空间分析，我们发现表达关键DOL标记（相应的SERPINA3N/SERPINA3）的少突胶质细胞存在于脑损伤区域的皮层中，并在a β斑块附近富集。在人死后脑组织中，该标记物的表达水平与认知能力下降相关。总之，本研究揭示了少突胶质细胞在中枢神经系统病理中的共同特征。我们在淀粉样变性的5xFAD模型中发现了与脑病理相关的少突胶质细胞特征，我们称之为疾病相关少突胶质细胞（DOLs）。发现这种特征在不同病理的少突胶质细胞中是共享的。
Alzheimer’s disease (AD) is a complex neurodegenerative disease, perturbing neuronal and non-neuronal cell populations. Here, using single-cell transcritpomics, we mapped all non-immune, non-neuronal cell populations in wild-type and AD model (5xFAD) mouse brains. We identified an oligodendrocyte state that increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). In a murine model of amyloidosis, DOLs appear long after plaque accumulation, and amyloid-beta (Aβ) alone was not sufficient to induce the DOL signature in vitro. DOLs could be identified in a mouse model of tauopathy and in other murine neurodegenerative and autoimmune inflammatory conditions, suggesting a common response to severe pathological conditions. Using quantitative spatial analysis of mouse and postmortem human brain tissues, we found that oligodendrocytes expressing a key DOL marker (SERPINA3N/SERPINA3 accordingly) are present in the cortex in areas of brain damage and are enriched near Aβ-plaques. In postmortem human brain tissue, the expression level of this marker correlated with cognitive decline. Altogether, the present study uncovers a shared signature of oligodendrocytes in central nervous system pathologies. We identified an oligodendrocyte signature associated with brain pathology in the 5xFAD model of amyloidosis, which we termed disease-associated oligodendrocytes (DOLs). This signature was found to be shared by oligodendrocytes across pathologies.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
影响因子：
46.9
作者：
Greenwald, Noah F.;Miller, Geneva;Moen, Erick;Kong, Alex;Kagel, Adam;Dougherty, Thomas;Fullaway, Christine Camacho;McIntosh, Brianna J.;Leow, Ke Xuan;Schwartz, Morgan Sarah;Pavelchek, Cole;Cui, Sunny;Camplisson, Isabella;Bar-Tal, Omer;Singh, Jaiveer;Fong, Mara;Chaudhry, Gautam;Abraham, Zion;Moseley, Jackson;Warshawsky, Shiri;Soon, Erin;Greenbaum, Shirley;Risom, Tyler;Hollmann, Travis;Bendall, Sean C.;Keren, Leeat;Graf, William;Angelo, Michael;Van Valen, David
通讯作者：
Van Valen, David
DOI：
10.1126/science.1247651
发表时间：
2014-02-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Jaitin DA;Kenigsberg E;Keren-Shaul H;Elefant N;Paul F;Zaretsky I;Mildner A;Cohen N;Jung S;Tanay A;Amit I
通讯作者：
Amit I
影响因子：
10.6
作者：
Karch CM;Goate AM
通讯作者：
Goate AM
影响因子：
25
作者：
Hasel, Philip;Rose, Indigo V. L.;Liddelow, Shane A.
通讯作者：
Liddelow, Shane A.