Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice.
T cells primarily drive the autoimmune destruction of pancreatic beta cells in Type 1 diabetes (T1D). However, the profound yet uncharacterized diversity of the T cell populations in vivo has hindered obtaining a clear picture of the T cell changes that occur longitudinally during T1D onset. This st...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0317987 |
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| author | Md Zohorul Islam Sam Zimmerman Alexis Lindahl Jon Weidanz Jose Ordovas-Montanes Aleksandar Kostic Jacob Luber Michael Robben |
| author_facet | Md Zohorul Islam Sam Zimmerman Alexis Lindahl Jon Weidanz Jose Ordovas-Montanes Aleksandar Kostic Jacob Luber Michael Robben |
| author_sort | Md Zohorul Islam |
| collection | DOAJ |
| description | T cells primarily drive the autoimmune destruction of pancreatic beta cells in Type 1 diabetes (T1D). However, the profound yet uncharacterized diversity of the T cell populations in vivo has hindered obtaining a clear picture of the T cell changes that occur longitudinally during T1D onset. This study aimed to identify T cell clonal expansion and distinct transcriptomic signatures associated with T1D progression in Non-Obese Diabetic (NOD) mice. Here we profiled the transcriptome and T cell receptor (TCR) repertoire of T cells at single-cell resolution from longitudinally collected peripheral blood and pancreatic islets of NOD mice using single-cell RNA sequencing technology. We detected disease dependent development of infiltrating CD8 + T cells with altered cytotoxic and inflammatory effector states. In addition, we discovered a high frequency of transcriptionally distinct double negative (DN) T cells that fluctuate throughout T1D pathogenesis. This study identifies potential disease relevant TCR sequences and potential disease biomarkers that can be further characterized through future research. |
| format | Article |
| id | doaj-art-3850fa8656cd4c449353430a078ffd66 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-3850fa8656cd4c449353430a078ffd662025-08-20T02:32:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031798710.1371/journal.pone.0317987Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice.Md Zohorul IslamSam ZimmermanAlexis LindahlJon WeidanzJose Ordovas-MontanesAleksandar KosticJacob LuberMichael RobbenT cells primarily drive the autoimmune destruction of pancreatic beta cells in Type 1 diabetes (T1D). However, the profound yet uncharacterized diversity of the T cell populations in vivo has hindered obtaining a clear picture of the T cell changes that occur longitudinally during T1D onset. This study aimed to identify T cell clonal expansion and distinct transcriptomic signatures associated with T1D progression in Non-Obese Diabetic (NOD) mice. Here we profiled the transcriptome and T cell receptor (TCR) repertoire of T cells at single-cell resolution from longitudinally collected peripheral blood and pancreatic islets of NOD mice using single-cell RNA sequencing technology. We detected disease dependent development of infiltrating CD8 + T cells with altered cytotoxic and inflammatory effector states. In addition, we discovered a high frequency of transcriptionally distinct double negative (DN) T cells that fluctuate throughout T1D pathogenesis. This study identifies potential disease relevant TCR sequences and potential disease biomarkers that can be further characterized through future research.https://doi.org/10.1371/journal.pone.0317987 |
| spellingShingle | Md Zohorul Islam Sam Zimmerman Alexis Lindahl Jon Weidanz Jose Ordovas-Montanes Aleksandar Kostic Jacob Luber Michael Robben Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. PLoS ONE |
| title | Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. |
| title_full | Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. |
| title_fullStr | Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. |
| title_full_unstemmed | Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. |
| title_short | Single-cell RNA-seq reveals disease-specific CD8+ T cell clonal expansion and a high frequency of transcriptionally distinct double-negative T cells in diabetic NOD mice. |
| title_sort | single cell rna seq reveals disease specific cd8 t cell clonal expansion and a high frequency of transcriptionally distinct double negative t cells in diabetic nod mice |
| url | https://doi.org/10.1371/journal.pone.0317987 |
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