Similar Datasets
Project description:CD8+ T cells play a pivotal role in restricting chronic virus infection and provide long-term protective immunity. The molecular mechanisms that govern long-term persistence of antiviral memory CD8+ T cells are poorly understood. Growth factor independent-1 (GFI1), a transcriptional repressor, plays a crucial role in T cell development. We show that following T cell activation, GFI1 expression is selectively maintained in memory CD8+ T cells, and GFI1 marks transcriptionally distinct antiviral CD8+ T cells with superior recall and expansion capacity. Conditional deletion of GFI1 in CD8+ T cells revealed that plays a crucial role in long-term persistence of CD8+ T cells responses following chronic virus infection. Single-cell multiome sequencing demonstrated that GFI1 epigenetically controls the gene regulatory networks that promote memory CD8+ T cell proliferation. GFI1 mediated eomesodermin expression protects the CD8+ T cells from activation induced cell death. Moreover, temporal mapping revealed that continuous GFI1 expression is required to maintain long-term memory CD8+ T cells persistence. Thus, GFI1 is central regulator of the molecular programs that shape memory features and is pivotal in promoting CD8+ T cell self-renewal and long-term protective memory formation.
2025-04-23 | GSE272025 | GEO
Project description:CD8+ T cells play a pivotal role in restricting chronic virus infection and provide long-term protective immunity. The molecular mechanisms that govern long-term persistence of antiviral memory CD8+ T cells are poorly understood. Growth factor independent-1 (GFI1), a transcriptional repressor, plays a crucial role in T cell development. We show that following T cell activation, GFI1 expression is selectively maintained in memory CD8+ T cells, and GFI1 marks transcriptionally distinct antiviral CD8+ T cells with superior recall and expansion capacity. Conditional deletion of GFI1 in CD8+ T cells revealed that plays a crucial role in long-term persistence of CD8+ T cells responses following chronic virus infection. Single-cell multiome sequencing demonstrated that GFI1 epigenetically controls the gene regulatory networks that promote memory CD8+ T cell proliferation. GFI1 mediated eomesodermin expression protects the CD8+ T cells from activation induced cell death. Moreover, temporal mapping revealed that continuous GFI1 expression is required to maintain long-term memory CD8+ T cells persistence. Thus, GFI1 is central regulator of the molecular programs that shape memory features and is pivotal in promoting CD8+ T cell self-renewal and long-term protective memory formation.
2025-04-23 | GSE271884 | GEO
Project description:CD8+ T cells play a pivotal role in restricting chronic virus infection and provide long-term protective immunity. The molecular mechanisms that govern long-term persistence of antiviral memory CD8+ T cells are poorly understood. Growth factor independent-1 (GFI1), a transcriptional repressor, plays a crucial role in T cell development. We show that following T cell activation, GFI1 expression is selectively maintained in memory CD8+ T cells, and GFI1 marks transcriptionally distinct antiviral CD8+ T cells with superior recall and expansion capacity. Conditional deletion of GFI1 in CD8+ T cells revealed that plays a crucial role in long-term persistence of CD8+ T cells responses following chronic virus infection. Single-cell multiome sequencing demonstrated that GFI1 epigenetically controls the gene regulatory networks that promote memory CD8+ T cell proliferation. GFI1 mediated eomesodermin expression protects the CD8+ T cells from activation induced cell death. Moreover, temporal mapping revealed that continuous GFI1 expression is required to maintain long-term memory CD8+ T cells persistence. Thus, GFI1 is central regulator of the molecular programs that shape memory features and is pivotal in promoting CD8+ T cell self-renewal and long-term protective memory formation.
2025-04-23 | GSE271768 | GEO
Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence
| PRJNA1133795 | ENA
Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [ATAC-seq].
| PRJNA1133801 | ENA
Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [RNA-seq]
| PRJNA1133060 | ENA
Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [scMultiome-seq].
| PRJNA1134667 | ENA
Project description:Alloreactive memory T cells, unlike naive T cells, fail to be restrained by transplantation tolerance protocols or regulatory T cells, and therefore represent a critical barrier to long-term graft acceptance. Using female mice sensitized by rejection of fully-mismatched paternal skin allografts, we show that subsequent semi-allogeneic pregnancy successfully reprograms memory fetus/graft-specific CD8+ T cells (TFGS) towards hypofunction in a manner that is mechanistically distinct from naive TFGS. Post-partum memory TFGS were durably hypofunctional, exhibiting enhanced susceptibility to transplantation tolerance induction. Furthermore, multi-omics studies revealed that pregnancy induced extensive phenotypic and transcriptional modifications in memory TFGS reminiscent of T cell exhaustion. Strikingly, at loci transcriptionally modified in both naive and memory TFGS during pregnancy, chromatin remodeling was observed exclusively in memory and not naive TFGS. These data reveal a novel link between T cell memory and hypofunction via exhaustion circuits and pregnancy-mediated epigenetic imprinting. This conceptual advance has immediate clinical relevance to pregnancy and transplantation tolerance.
| S-EPMC10104270 | biostudies-literature
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 assay for transposase-accessible chromatin using sequencing confirmed the coexistence 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 use of this methylation-based multipotency index for investigating human and mouse CD8+ T cell differentiation.
| S-EPMC7183435 | biostudies-literature
Project description:Transcription repressor BACH2 redirects short-lived terminally differentiated effector into long-lived memory cells. We postulate that BACH2-mediated long-lived memory programs promote HIV-1 persistence in gut CD4+ T cells. We coupled single-cell DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA and HIV-1 RNA in 100,744 gut T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors. BACH2 was the leading transcription factor that shaped gut tissue resident memory T cells (TRMs) into long-lived memory with restrained interferon-induced effector function. We found that HIV-1-infected cells were enriched in TRMs (80.8%). HIV-1-infected cells had increased BACH2 transcription factor accessibility, TRM (CD49a, CD69, CD103) and survival (IL7R) gene expression, and Th17 polarization (RORC, CCR6). In vitro gut CD4+ T cell infection revealed preferential infection and persistence of HIV-1 in CCR6+ TRMs. Overall, we found BACH2-driven TRM program promotes HIV-1 persistence and BACH2 as a new therapeutic target.
| S-EPMC11702684 | biostudies-literature