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Cell type-specific vulnerability to traumatic brain injury

C.E. Credits: P.A.C.E. CE Florida CE
Speaker
  • Sr. Postdoctoral Researcher Laboratory of Glia Biology, VIB-KU Leuven Center for Brain and Disease Research
    Biography

      Dr. Araks Martirosyan is a sr. postdoctoral researcher in the Laboratory of Glia Biology at the VIB-KU Leuven Center for Brain and Disease Research (Belgium). After Finishing her B.Sc. in the Faculty of Physics at Yerevan State University (Armenia) and M.Sc. in Applied Physics at Cergy-Pontoise University (France), she became interested in the application of Statistical Physics to Biology and chose Computational Biology as her future research direction. Dr. Martirosyan received her Ph.D. from the Sapienza University of Rome (Italy) in 2016. Shortly after she joined the VIB-KU Leuven Laboratory of Glia Biology headed by Prof. Matthew Holt, where she investigates the molecular heterogeneity of astrocytes - a major non-neuronal cell type in the brain, whose therapeutic potential is largely overlooked. Combining cutting edge single cell RNA-seq and novel spatial transcriptomics technologies, Dr. Martirosyan was amongst the first to describe unique astrocyte subtypes in the brain. The goal of her current work is to understand how these subtypes respond to injury and/or disease.


    Abstract

    Traumatic brain injury (TBI) is best characterized as brain dysfunction caused by an outside force, usually a violent blow to the head, often occurring as a result of a severe sports injury or car accident. It is a major global health concern, affecting 69 million people worldwide per year, and is one of the most common causes of disability and death in adults. Nearly 50% of TBI patients experience long term cognitive impairment, linked to hippocampal neuronal damage and death. At the same time a deregulation of the hippocampal neurogenic processes is observed which impedes possible functional recovery of the brain. In particular, immunohistochemistry in mouse hippocampus has shown that cortical TBI affects neural stem and progenitor cells (NSPCs) residing in sub-granular zone of dendrite gyrus. Moreover, severe changes in the states of astrocytes, cells regulating axonal growth and synaptogenesis, has been observed throughout hippocampus. Here, in a collaborative project between VIB-KU Leuven, University of Amsterdam and the Bioinformatics CRO, we explore the cellular response in hippocampus following cortical TBI, exploiting cutting edge single cell RNA sequencing (10X Genomics) and highly multiplexed in situ hybridization (Resolve Biosciences) technologies. We systematically assess the sensitivity of NSPCs, immature astrocytes and immature neurons located in the sub-granular layer of dentate gyrus to TBI-induced pathology at the molecular level. We further characterize molecular changes within the hippocampus and the surrounding tissue, providing a spatial map of gene expression changes with single cell resolution.

    Learning Objectives:

    1. Single cell and spatial transcriptomics to investigate cell type heterogeneity at the highest resolution.

    2. The impact of cortical traumatic brain injury on hippocampus and the surrounding tissue.

    3. Effects of traumatic brain injury on neural stem and progenitor cells.


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