Single cell molecular alterations reveal target cells and pathways of concussive brain injury

Douglas Arneson, Guanglin Zhang, Zhe Ying, Yumei Zhuang, Hyae Ran Byun, In Sook Ahn, Fernando Gomez-Pinilla () and Xia Yang ()
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Douglas Arneson: University of California, Los Angeles
Guanglin Zhang: University of California, Los Angeles
Zhe Ying: University of California, Los Angeles
Yumei Zhuang: University of California, Los Angeles
Hyae Ran Byun: University of California, Los Angeles
In Sook Ahn: University of California, Los Angeles
Fernando Gomez-Pinilla: University of California, Los Angeles
Xia Yang: University of California, Los Angeles

Nature Communications, 2018, vol. 9, issue 1, 1-18

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06222-0

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