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| Status |
Public on Sep 02, 2020 |
| Title |
Transcriptomic and clonal characterization of T cells in the human central nervous system |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Tissues develop unique homeostatic immune states through specific recruitment of immune cells that are further shaped by the tissue environment. Here, we use single-cell RNA and TCR sequencing of healthy cerebrospinal fluid (CSF) and single-nucleus RNA sequencing of brain parenchyma to profile the T cell state in the human central nervous system (CNS). We observe a continuum of T cell states, reflecting a blood-CSF “axis”, that we use to reveal that T cells in the CSF largely exhibit a tissue-resident phenotype with a balance of co-inhibitory and effector function gene expression, including PD-1+ T cells retaining the ability to produce IFNg. Leveraging paired single-cell TCR sequencing to identify clonal T cell groups, we find that T cell phenotypes mirror the tissue where they reside and that clonally-expanded T cells reflect the most CSF-distinct state. To identify how this T cell state is perturbed during neuroinflammation, we profiled newly-diagnosed, treatment-naive patients with multiple sclerosis (MS) and observed that clonally expanded T cells are the most phenotypically different between patients and healthy controls. We then identify putative pathways of communication between T cells in the brain parenchyma and glia and neurons that may be involved in shaping T cell function. Our elucidation of the CNS T cell state provides context for understanding neuroinflammation and neurodegeneration as well as providing a framework for understanding tissue-driven T cell adaptation.
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| Overall design |
This series includes only single nucleus RNA Sequencing. The TCR-seq data were submitted to dbGaP.
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| Contributor(s) |
Hafler DA, Zhang L, Pappalardo JL, van Dijk D |
| Citation(s) |
32948672 |
| Submission date |
Sep 01, 2020 |
| Last update date |
Feb 01, 2021 |
| Contact name |
Le Zhang |
| E-mail(s) |
le.zhang@yale.edu
|
| Organization name |
Yale University
|
| Department |
Neurology
|
| Street address |
300 George Street
|
| City |
New Haven |
| State/province |
CT |
| ZIP/Postal code |
06510 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA660743 |
| SRA |
SRP279608 |
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