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    Single-Nucleus Multi-Omic Characterization of Age-Specific Effects of Traumatic Brain Injury in the Mouse Hippocampus

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    Author
    Bhatia, Parth cc
    Advisor
    Ament, Seth A.
    Date
    2022
    Type
    dissertation
    
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    Abstract
    Traumatic brain injury (TBI) has been characterized as a silent epidemic with growing incidence rates worldwide. Recently, single cell genomics has revealed multiple microglial subtypes activated during inflammation, and emerging evidence suggests that distinct subtypes contribute to age-related differences in neurodegeneration and neuroprotection. In this thesis, I test the hypothesis that differential microglial activation states contribute to the worsened outcomes to TBI associated with aging. Using single-nucleus RNA and ATAC sequencing, I describe cell type specific transcriptional and epigenomic changes in microglia in the context of TBI in young vs. aged mice. I found substantial transcriptional effects of TBI in microglia in both young and aged mice. Regulatory network models predict common repression of homeostatic genes but differential activation of regulatory activity with transcription factors like Nfe2l2 and Runx1 in rescuing and repressing a neuroprotective state of microglia.
    Description
    University of Maryland, Baltimore. Human Genetics. M.S. 2022.
    Keyword
    Solitary Nucleus
    Age Factors
    Brain Injuries, Traumatic
    Hippocampus
    Mice
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/20365
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