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

Author

Listed:
  • Douglas Arneson

    (University of California, Los Angeles
    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
    University of California, Los Angeles
    University of California, Los Angeles)

  • Xia Yang

    (University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles
    University of California, Los Angeles)

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.

Suggested Citation

  • Douglas Arneson & Guanglin Zhang & Zhe Ying & Yumei Zhuang & Hyae Ran Byun & In Sook Ahn & Fernando Gomez-Pinilla & Xia Yang, 2018. "Single cell molecular alterations reveal target cells and pathways of concussive brain injury," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06222-0
    DOI: 10.1038/s41467-018-06222-0
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    Cited by:

    1. Hadi Abou-El-Hassan & Rafael M. Rezende & Saef Izzy & Galina Gabriely & Taha Yahya & Bruna K. Tatematsu & Karl J. Habashy & Juliana R. Lopes & Gislane L. V. Oliveira & Amir-Hadi Maghzi & Zhuoran Yin &, 2023. "Vγ1 and Vγ4 gamma-delta T cells play opposing roles in the immunopathology of traumatic brain injury in males," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. P. Bielefeld & A. Martirosyan & S. Martín-Suárez & A. Apresyan & G. F. Meerhoff & F. Pestana & S. Poovathingal & N. Reijner & W. Koning & R. A. Clement & I. Veen & E. M. Toledo & O. Polzer & I. Durá &, 2024. "Traumatic brain injury promotes neurogenesis at the cost of astrogliogenesis in the adult hippocampus of male mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Rosa M S Visscher & Nina Feddermann-Demont & Fausto Romano & Dominik Straumann & Giovanni Bertolini, 2019. "Artificial intelligence for understanding concussion: Retrospective cluster analysis on the balance and vestibular diagnostic data of concussion patients," PLOS ONE, Public Library of Science, vol. 14(4), pages 1-15, April.

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