Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (NOD EVs)
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ABSTRACT:
PROVIDER: PRJNA1013949 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25940268.fastq.gz | Fastqsanger.gz | |||
| SRR25940269.fastq.gz | Fastqsanger.gz | |||
| SRR25940270.fastq.gz | Fastqsanger.gz |
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Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242565 | GEO
Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242567 | GEO
Project description:Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis (NOD islets)
| PRJNA1013951 | ENA
Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242561 | GEO
Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242566 | GEO
Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242564 | GEO
Project description:Transfer RNAs (tRNAs) play a central and well recognized role in protein synthesis. Recent studies revealed that these molecules can be cleaved to generate tRNA fragments (tRFs) with regulatory functions. Here, we studied the contribution of tRFs to pancreatic β-cell loss during the initial phases of type 1 diabetes (T1D), an autoimmune disorder characterized by the invation of immune cells in the pancreas and progressive loss of insulin-secreting cells. Small RNA-profiling showed that the pool of tRFs present in pancreatic β-cells is altered in non-obese diabetic (NOD) mice, a mouse model used to study T1D. We found that part of these changes is triggered by the exposure of β-cells to proinflammatory cytokines released during the autoimmune reaction while others result from the direct transfer of tRFs from autoreactive T lymphocytes to insulin-secreting cells via extracellular vesicles. Indeed, using an RNA-tagging approach, we could demonstrate that a group of tRFs are transferred in vivo in from CD4+CD25- T lymphocytes to pancreatic β-cells, upon T cell adoptive transfer in NOD scid mice. Morevoer, the up-regulation of selected tRFs associated with the autoimmune reaction triggers β-cell apoptosis and gene expression changes that affect the immune regulatory capacity of β-cells. Our data point to tRFs as novel players in type 1 diabetes and potentially in other autoimmune disorders.
2024-05-24 | GSE242563 | GEO
Project description:Role of tRNA-derived fragments in the cross-talk between immune cells and beta cells during type 1 diabetes pathogenesis
| PRJNA1013941 | ENA
Project description:Aims/hypothesistRNAs play a central role in protein synthesis. Besides this canonical function, they were recently found to generate non-coding RNA fragments (tRFs) regulating different cellular activities. The aim of this study was to assess the involvement of tRFs in the crosstalk between immune cells and beta cells and to investigate their contribution to the development of type 1 diabetes.MethodsGlobal profiling of the tRFs present in pancreatic islets of 4- and 8-week-old NOD mice and in extracellular vesicles released by activated CD4+ T lymphocytes was performed by small RNA-seq. Changes in the level of specific fragments were confirmed by quantitative PCR. The transfer of tRFs from immune cells to beta cells occurring during insulitis was assessed using an RNA-tagging approach. The functional role of tRFs increasing in beta cells during the initial phases of type 1 diabetes was determined by overexpressing them in dissociated islet cells and by determining the impact on gene expression and beta cell apoptosis.ResultsWe found that the tRF pool was altered in the islets of NOD mice during the initial phases of type 1 diabetes. Part of these changes were triggered by prolonged exposure of beta cells to proinflammatory cytokines (IL-1β, TNF-α and IFN-γ) while others resulted from the delivery of tRFs produced by CD4+ T lymphocytes infiltrating the islets. Indeed, we identified several tRFs that were enriched in extracellular vesicles from CD4+/CD25- T cells and were transferred to beta cells upon adoptive transfer of these immune cells in NOD.SCID mice. The tRFs delivered to beta cells during the autoimmune reaction triggered gene expression changes that affected the immune regulatory capacity of insulin-secreting cells and rendered the cells more prone to apoptosis.Conclusions/interpretationOur data point to tRFs as novel players in the crosstalk between the immune system and insulin-secreting cells and suggest a potential involvement of this novel class of non-coding RNAs in type 1 diabetes pathogenesis.Data availabilitySequences are available from the Gene Expression Omnibus (GEO) with accession numbers GSE242568 and GSE256343.
| S-EPMC11446995 | biostudies-literature
Project description:Cytosolic and mitochondrial fragments that arise from the cleavage of tRNAs and mt-tRNAs, respectively, have been identified as potential novel regulators of cellular functions. In this study we identified hundreds of fragments in the pancreatic islets of healthy human individuals. We were able to annotate 3593 tRFs (16-55 base pairs) present in the islets of healthy human individuals (we considered a minimum of 5 cpm values in each of the 3 samples). Interestingly, the vast majority of the tRFs whose levels are altered in pancreatic islets of prediabetic NOD mice and in extracellular vesicles released by activated CD4+ T lymphocytes, are conserved in humans and were detected in human pancreatic islets. This suggests a possible conservation of the findings of this study in a human context.
2024-05-14 | GSE256343 | GEO