Single cell RNA (scRNAseq) and T cell receptor sequencing (scTCRseq) of cerebrospinal fluid (CSF) samples from three patients with spinal cord injury (SCI) [TCR-seq]
Ontology highlight
ABSTRACT: The CSF encompasses a highly controlled immune system. However, little is known about the alterations in CSF immune microenvironment after SCI. Here, we performed scRNA and TCRseq on CSF collected from three SCI patients caused by car accidents to analyze the transcriptomic changes of CSF immune cells.
Project description:The CSF encompasses a highly controlled immune system. However, little is known about the alterations in CSF immune microenvironment after SCI. Here, we performed scRNA and TCRseq on CSF collected from three SCI patients caused by car accidents to analyze the transcriptomic changes of CSF immune cells.
Project description:Cerebrospinal fluid (CSF) contains a tightly regulated, specialized immune system. Yet, little is known about how aging influences CSF immunity in cognitively typical versus cognitively impaired individuals. Here, we performed single cell RNA sequencing (scRNAseq) on CSF collected from 45 cognitively typical subjects ranging from 54-82 years old. We then assessed age-related transcriptomic changes using several bioinformatic approaches, including linear and local polynomial regression. We reveal pronounced changes to several CSF immune cell types that occur around age 75, including alterations to clonally expanded T cells and activated monocytes. We then compared CSF immune systems from cognitively typical subjects to 14 subjects with mild cognitive impairment or Alzheimer’s disease. Our results indicate disparate age-related CSF immune system perturbations in cognitively impaired subjects. These results highlight the potential to utilize CSF immune changes to identify age-related neuroinflammation in cognitively impaired individuals.
Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration
Project description:Single cell RNA (scRNAseq) and T cell receptor sequencing (scTCRseq) of cerebrospinal fluid (CSF) samples from three patients with spinal cord injury (SCI) [TCR-seq]
Project description:Single cell RNA (scRNAseq) and T cell receptor sequencing (scTCRseq) of cerebrospinal fluid (CSF) samples from three patients with spinal cord injury (SCI) [scRNA-seq]
Project description:To study the regulation of candidate genes from our study in human cells, we analyzed CD4+ T cells from blood and CSF of MA patients and age and sex matched idiopathic intracranial hypertension controls We analyzed 40845 cells in control blood, 807 cells in control CSF, 29749 cells in MS blood and 15768 cells in MS CSF