GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1133795 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29747600_1.fastq.gz | Fastqsanger.gz | |||
| SRR29747600_2.fastq.gz | Fastqsanger.gz | |||
| SRR29747601_1.fastq.gz | Fastqsanger.gz | |||
| SRR29747601_2.fastq.gz | Fastqsanger.gz | |||
| SRR29747602_1.fastq.gz | Fastqsanger.gz |
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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.
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Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [ATAC-seq].
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Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [RNA-seq]
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Project description:GFI1-driven transcriptional and epigenetic programs maintain memory CD8+ T cell persistence [scMultiome-seq].
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2025-04-23 | GSE271885 | GEO
Project description:Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a common integration site in Moloney-murine-leukemia-virus-induced T-cell leukemia. Gfi1-/- mice display increased apoptosis of developing thymocytes and T lymphopenia; however, there are contradictory reports of the absolute number of Gfi1-/- early T lineage progenitors. We used floxed alleles of Gfi1 crossed to various T-cell-specific Cre transgenes to map the requirements for Gfi1 during lymphoid priming and development. We show that Gfi1 is necessary for the proper formation and function of both lymphoid-primed multipotent progenitors and early T lineage progenitors. These defects correlate with a global inability of Gfi1-/- progenitors to enforce the activation of lymphoid genes including IL7R, Rag1, Flt3 and Notch1. Forced expression of intracellular Notch1 fails to rescue the Gfi1-/- defective lymphoid gene signature or Gfi1-/- T cell development. Instead, activation of Notch1 in Gfi1-/- cells results in a potent synthetic lethal phenotype that is most dramatic in immature thymocytes, but absent in mature peripheral T cells where developmental transcriptional programs are silent. Moreover, we find that the requirement for Gfi1-transcriptional integration of Notch-driven lymphoid transcriptional programs is cell autonomous. Our data indicate that Gfi1 is required at multiple independent stages of lymphoid development. In hematopoietic progenitors Gfi1 is necessary to integrate Notch1 signaling, mediate lymphoid priming, the formation of early T lineage progenitors and subsequent T lineage commitment. Lineage negative cells were purified by magnetic beads from RosaCreERT2 Gfi1 ex4-5 floxed mice and an activated Notch1 signal was introduced using a GFP+ retroviral vector. GFP+ progenitors were FACS-sorted and cultured in semi-solid media for one week to allow sufficient time to to instruct lymphoid differentiation, then replated in 1uM 4-OHT or EtOH control. After an additional 7 days, CFU were disrupted and RNA was isolated for global gene expression using microarrays.
2014-10-01 | E-GEOD-41162 | biostudies-arrayexpress
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.
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Project description:Growth factor independent 1 (Gfi1) is a transcriptional repressor originally identified as a common integration site in Moloney-murine-leukemia-virus-induced T-cell leukemia. Gfi1-/- mice display increased apoptosis of developing thymocytes and T lymphopenia; however, there are contradictory reports of the absolute number of Gfi1-/- early T lineage progenitors. We used floxed alleles of Gfi1 crossed to various T-cell-specific Cre transgenes to map the requirements for Gfi1 during lymphoid priming and development. We show that Gfi1 is necessary for the proper formation and function of both lymphoid-primed multipotent progenitors and early T lineage progenitors. These defects correlate with a global inability of Gfi1-/- progenitors to enforce the activation of lymphoid genes including IL7R, Rag1, Flt3 and Notch1. Forced expression of intracellular Notch1 fails to rescue the Gfi1-/- defective lymphoid gene signature or Gfi1-/- T cell development. Instead, activation of Notch1 in Gfi1-/- cells results in a potent synthetic lethal phenotype that is most dramatic in immature thymocytes, but absent in mature peripheral T cells where developmental transcriptional programs are silent. Moreover, we find that the requirement for Gfi1-transcriptional integration of Notch-driven lymphoid transcriptional programs is cell autonomous. Our data indicate that Gfi1 is required at multiple independent stages of lymphoid development. In hematopoietic progenitors Gfi1 is necessary to integrate Notch1 signaling, mediate lymphoid priming, the formation of early T lineage progenitors and subsequent T lineage commitment.
2014-10-01 | GSE41162 | GEO