Altered oligodendroglia and astroglia in chronic traumatic encephalopathy.
Altered oligodendroglia and astroglia in chronic traumatic encephalopathy.
复制标题
DOI：
10.1007/s00401-021-02322-2
复制
发表时间：
2021-08
影响因子：
12.7
通讯作者：
McKee AC
中科院分区：
文献类型：
--
作者：
Chancellor KB;Chancellor SE;Duke-Cohan JE;Huber BR;Stein TD;Alvarez VE;Okaty BW;Dymecki SM;McKee AC
慢性创伤性脑病（CTE）是一种在接触性运动员，退伍军人和其他暴露于重复头部撞击的人中发现的进行性tau蛋白病。白色物质稀疏和轴突损失已在CTE中报道，但尚未在分子或细胞水平上表征。在这里，我们提出的RNA测序概况的细胞核从死后背外侧额叶白色的问题，从8个人与神经病理学证实CTE和8个年龄和性别匹配的控制。使用无偏聚类方法分析这些概况，我们鉴定了18个转录组学上不同的细胞组（簇），反映了细胞类型和/或细胞状态，其中一个子集显示CTE和对照组织之间的差异。在与单核RNA-seq工作中使用的组织切片相邻的组织切片上应用的独立原位方法产生了类似的发现。发现少突胶质细胞在CTE白色物质样品中受到最严重的影响;它们在数量上减少，并且在亚型簇中的相对比例发生改变。此外，CTE富集的少突胶质细胞群体显示出更丰富的与铁代谢和细胞应激反应相关的转录物。CTE组织在组织学上也表现出过度的铁积累。在星形胶质细胞中，CTE和对照样品之间的总细胞数无法区分，但与对照相比，CTE星形胶质细胞组中与神经炎症相关的转录物升高。这些结果表明CTE少突胶质细胞和星形胶质细胞的特定分子和细胞差异，并表明白色物质的改变是CTE神经变性的一个重要方面。在线版本包含补充材料，可通过10.1007/s 00401 -021-02322-2获得。
Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head impacts. White matter rarefaction and axonal loss have been reported in CTE but have not been characterized on a molecular or cellular level. Here, we present RNA sequencing profiles of cell nuclei from postmortem dorsolateral frontal white matter from eight individuals with neuropathologically confirmed CTE and eight age- and sex-matched controls. Analyzing these profiles using unbiased clustering approaches, we identified eighteen transcriptomically distinct cell groups (clusters), reflecting cell types and/or cell states, of which a subset showed differences between CTE and control tissue. Independent in situ methods applied on tissue sections adjacent to that used in the single-nucleus RNA-seq work yielded similar findings. Oligodendrocytes were found to be most severely affected in the CTE white matter samples; they were diminished in number and altered in relative proportions across subtype clusters. Further, the CTE-enriched oligodendrocyte population showed greater abundance of transcripts relevant to iron metabolism and cellular stress response. CTE tissue also demonstrated excessive iron accumulation histologically. In astrocytes, total cell numbers were indistinguishable between CTE and control samples, but transcripts associated with neuroinflammation were elevated in the CTE astrocyte groups compared to controls. These results demonstrate specific molecular and cellular differences in CTE oligodendrocytes and astrocytes and suggest that white matter alterations are a critical aspect of CTE neurodegeneration. The online version contains supplementary material available at 10.1007/s00401-021-02322-2.
登录
查看更多内容
影响因子：
3.2
作者：
Bieniek KF;Cairns NJ;Crary JF;Dickson DW;Folkerth RD;Keene CD;Litvan I;Perl DP;Stein TD;Vonsattel JP;Stewart W;Dams-O'Connor K;Gordon WA;Tripodis Y;Alvarez VE;Mez J;Alosco ML;McKee AC;TBI/CTE Research Group
通讯作者：
TBI/CTE Research Group
影响因子：
17.1
作者：
Goldstein LE;Fisher AM;Tagge CA;Zhang XL;Velisek L;Sullivan JA;Upreti C;Kracht JM;Ericsson M;Wojnarowicz MW;Goletiani CJ;Maglakelidze GM;Casey N;Moncaster JA;Minaeva O;Moir RD;Nowinski CJ;Stern RA;Cantu RC;Geiling J;Blusztajn JK;Wolozin BL;Ikezu T;Stein TD;Budson AE;Kowall NW;Chargin D;Sharon A;Saman S;Hall GF;Moss WC;Cleveland RO;Tanzi RE;Stanton PK;McKee AC
通讯作者：
McKee AC
影响因子：
16.6
作者：
Arneson D;Zhang G;Ying Z;Zhuang Y;Byun HR;Ahn IS;Gomez-Pinilla F;Yang X
通讯作者：
Yang X
影响因子：
3.2
作者：
Doherty, Colin P.;O'Keefe, Eoin;Campbell, Matthew
通讯作者：
Campbell, Matthew
影响因子：
25
作者：
Hrvatin S;Hochbaum DR;Nagy MA;Cicconet M;Robertson K;Cheadle L;Zilionis R;Ratner A;Borges-Monroy R;Klein AM;Sabatini BL;Greenberg ME
通讯作者：
Greenberg ME