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.

中文翻译：

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单细胞分子改变揭示了脑震荡性脑损伤的靶细胞和通路。

考虑到受影响的大脑区域（如海马）的复杂细胞结构，创伤性脑损伤 (TBI) 的复杂神经病理学很难剖析。TBI 期间的海马功能障碍导致认知能力下降，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。使用无偏见的单细胞测序方法 Drop-seq，我们报告说，除了经典的海马细胞类型之外，震荡性 TBI 还会影响以前未定义的细胞群。TBI 还影响细胞类型特异性基因和通路，并改变细胞类型间的基因共表达，表明隐藏的致病机制和治疗靶点通路。根据 T4 转运蛋白转甲状腺素蛋白 Ttr 的信息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 和相关疾病治疗的致病途径增加了新的见解。