Single cell molecular alterations reveal target cells and pathways of concussive brain injury.
Single cell molecular alterations reveal target cells and pathways of concussive brain injury.
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DOI：
10.1038/s41467-018-06222-0
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发表时间：
2018-09-25
影响因子：
16.6
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Arneson D;Zhang G;Ying Z;Zhuang Y;Byun HR;Ahn IS;Gomez-Pinilla F;Yang X
创伤性脑损伤（TBI）复杂的神经病理学是难以解剖的，因为受影响的大脑区域如海马的细胞结构错综复杂。脑外伤期间的海马功能障碍导致认知能力下降，并可能升级为其他神经系统疾病，其分子基础隐藏在单个细胞的基因组程序中。使用无偏单细胞测序方法Drop-seq，我们报告了震荡性脑损伤影响以前未定义的细胞群，除了经典的海马细胞类型。TBI还影响细胞类型特异性基因和通路，改变细胞类型间基因共表达，提示潜在的致病机制和治疗靶点通路。通过T4转运体转甲状腺素Ttr调节甲状腺激素通路可减轻tbi相关的基因组和行为异常。因此，单细胞基因组学提供了关于TBI如何影响不同海马细胞类型的独特信息，为TBI和相关疾病的治疗方法提供了新的见解。创伤性脑损伤（TBI）影响海马体，并可导致神经和精神疾病。在这里，作者进行单细胞RNA测序，以揭示在TBI期间受影响的一系列细胞类型的分子途径。
The complex neuropathology of traumatic brain injury (TBI) is difficult to dissect, given the convoluted cytoarchitecture of affected brain regions such as the hippocampus. Hippocampal dysfunction during TBI results in cognitive decline that may escalate to other neurological disorders, the molecular basis of which is hidden in the genomic programs of individual cells. Using the unbiased single cell sequencing method Drop-seq, we report that concussive TBI affects previously undefined cell populations, in addition to classical hippocampal cell types. TBI also impacts cell type-specific genes and pathways and alters gene co-expression across cell types, suggesting hidden pathogenic mechanisms and therapeutic target pathways. Modulating the thyroid hormone pathway as informed by the T4 transporter transthyretin Ttr mitigates TBI-associated genomic and behavioral abnormalities. Thus, single cell genomics provides unique information about how TBI impacts diverse hippocampal cell types, adding new insights into the pathogenic pathways amenable to therapeutics in TBI and related disorders. Traumatic brain injury (TBI) affects the hippocampus and can lead to neurological and psychiatric disorders. Here, the authors perform single-cell RNA sequencing to reveal molecular pathways across a range of cell types affected during TBI.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
14.8
作者：
Brewer, Gregory J.;Torricelli, John R.
通讯作者：
Torricelli, John R.
影响因子：
81.5
作者：
Blennow, Kaj;Brody, David L.;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik
DOI：
10.1073/pnas.012425299
发表时间：
2002-01-08
影响因子：
11.1
作者：
Ino, Y;Gotoh, M;Hirohashi, S
通讯作者：
Hirohashi, S
影响因子：
48
作者：
Habib N;Avraham-Davidi I;Basu A;Burks T;Shekhar K;Hofree M;Choudhury SR;Aguet F;Gelfand E;Ardlie K;Weitz DA;Rozenblatt-Rosen O;Zhang F;Regev A
通讯作者：
Regev A