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Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (scATAC-seq)

ABSTRACT: Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (scATAC-seq)

PROVIDER: PRJNA604598 | ENA |

REPOSITORIES: ENA

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Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes

Project description:Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes

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Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (scATAC-seq)

Project description:The pool of beta cell-specific CD8+ T-cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell “multipotency index” and found that beta cell-specific CD8+ T-cells retained a stem-like epigenetic multipotency score. Single cell ATAC-seq analysis confirmed the co-existence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T-cells. Assessment of beta cell-specific CD8+ T-cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T-cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses, and document the utility of this novel methylation-based multipotency index for investigating human and mouse CD8+ T-cell differentiation.

2020-04-07 | GSE144692 | GEO

Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (WGBS)

Project description:Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (WGBS)

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Beta cell-specific CD8+ T cells maintain stem-cell memory-associated epigenetic programs during type 1 diabetes (WGBS)

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Maternal diabetes alters transcriptional programs in the developing embryo.

Project description:Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs. We compared E10.5 cntrol embryos to E10.5 embryos from diabetic pregnancies in the FVB mouse strain. Diabetes was induced in 7-9 week old female FVB mice by streptozotocin. Dams whose blood glucose levels exceeded 250 mg/dl were set up for mating. Embryos were dissected at E10.5 and total RNA was isolated. Equal amounts of RNA prepared from 3 individual embryos were pooled into one sample; each embryo was from a different pregnancy. Three pools were constructed for a total of nine embryos from diabetic pregnancies, and independently three pools for control embryos.

2012-09-25 | E-GEOD-41095 | biostudies-arrayexpress

Maternal diabetes alters transcriptional programs in the developing embryo.

2012-09-25 | GSE41095 | GEO

Cyclical macrophage plasticity provides periodic inflammatory and regenerative gene expression programs in cell cycle [scATAC-seq]

Project description:Cyclical macrophage plasticity provides periodic inflammatory and regenerative gene expression programs in cell cycle [scATAC-seq]

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Single-cell chromatin accessibility data using scATAC-seq

Project description:Cell-to-cell variation is a universal feature of life that impacts a wide range of biological phenomena, from developmental plasticity to tumor heterogeneity. While recent advances have improved our ability to document cellular phenotypic variation the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of cellular DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells via assay of transposase accessible chromatin sequencing (ATAC-seq). Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single-cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provides insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type specific accessibility variance across 6 cell types. Targeted perturbations of cell cycle or transcription factor signaling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome topological domains de novo, linking single-cell accessibility variation to three-dimensional genome organization. All together, single-cell analysis of DNA accessibility provides new insight into cellular variation of the “regulome.” Profiles of single cell epigenomes, assayed using scATAC-seq, across 8 cell types and 4 targeted cell manipulations. The complete data set contains a total of 1,632 assayed wells.

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Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk

Project description:Single-cell chromatin accessibility identifies pancreatic islet cell type- and state-specific regulatory programs of diabetes risk

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A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance [scATAC]

Project description:scATAC-seq datasets of immune cells in K392R and WT mice

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