A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations
Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of...
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| Published in | The Journal of clinical investigation Vol. 135; no. 1; pp. 1 - 19 |
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| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
American Society for Clinical Investigation
01.01.2025
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. |
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| AbstractList | Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG + dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. A compendium of single cell transcriptomics applied to cerebrospinal fluid for elucidating the pathophysiological characteristics of immune cells in central nervous system diseases. Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of [AREG.sup.+] dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases.Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases. |
| Audience | Academic |
| Author | Artyomov, Maxim N. Firulyova, Maria Schwarzkopf, Elizabeth A. Terekhova, Marina Abdalla, Nada M. Wu, Gregory F. Cantoni, Claudia Smirnov, Roman A. Edelson, Brian T. Sabatino, Joseph J. Meyer zu Hörste, Gerd Andhey, Prabhakar S. Schwab, Nicholas Kleverov, Maksim Liu, Kang Cross, Anne H. Esaulova, Ekaterina Bradstreet, Tara R. |
| AuthorAffiliation | 3 Weill Institute for Neurosciences, UCSF, San Francisco, California, USA 6 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA 5 Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany 7 Neurology Service, Veterans Affairs St. Louis Health Care System, St. Louis, Missouri, USA 2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA 1 Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona USA 4 Regeneron Pharmaceuticals, Tarrytown, New York, USA |
| AuthorAffiliation_xml | – name: 1 Department of Translational Neuroscience, Barrow Neurological Institute, Phoenix, Arizona USA – name: 2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA – name: 4 Regeneron Pharmaceuticals, Tarrytown, New York, USA – name: 6 Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA – name: 7 Neurology Service, Veterans Affairs St. Louis Health Care System, St. Louis, Missouri, USA – name: 3 Weill Institute for Neurosciences, UCSF, San Francisco, California, USA – name: 5 Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39744938$$D View this record in MEDLINE/PubMed |
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| Keywords | Innate immunity Neuroscience Adaptive immunity Immunology Neurological disorders |
| Language | English |
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| Snippet | Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary... |
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| SubjectTerms | Adult Aged Alzheimer Disease - cerebrospinal fluid Alzheimer Disease - immunology Alzheimer's disease Autoimmune diseases Central nervous system Cerebrospinal fluid COVID-19 COVID-19 - cerebrospinal fluid COVID-19 - immunology Datasets Dendritic cells Dendritic Cells - immunology Diagnosis Disease Encephalitis Female Genetic aspects Humans Immune system Immunologic diseases Lymphocytes Male Microglia Microglia - immunology Middle Aged Movement disorders Multiple sclerosis Multiple Sclerosis - cerebrospinal fluid Multiple Sclerosis - immunology Nervous system Nervous system diseases Neurodegenerative diseases Neurological diseases Parkinson Disease - cerebrospinal fluid Parkinson Disease - genetics Parkinson Disease - immunology Parkinson's disease Puncture Risk factors SARS-CoV-2 - immunology Single-Cell Analysis Spine Transcriptome Transcriptomics |
| Title | A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations |
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