Gene regulatory network determinants of rapid recall in human memory T cells [WGS]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE287942 | GEO | 2026/01/05
REPOSITORIES: GEO
Similar Datasets
Project description:Rapid recall is the hallmark of memory T cells. While naïve T cells require days to mount an effector response to a new threat, antigen-experienced memory T cells can produce cytokines within hours of the repeatencounter. The establishment of memory and control of rapid recall across lifespan is poorly understood, yet the mechanisms are fundamental to pathogen defense and immunological diseases. Epigenetic poising is a likely mechanism. Indeed, compared to naïve, memory cells exhibit enhanced chromatin accessibility proximal to rapid recall genes, but the transcription factors (TFs) that establish, maintain and utilize these putative regulatory elements are unknown. Here, we leverage single-nuclei (sn)multiome-seq (simultaneous snRNA-seq and snATAC-seq) to (1) characterize the dynamic activation responses of naïve and memory CD4+ T cell subsets and (2) reconstruct the underlying gene regulatory networks, at genome scale. Our analysis uncovered thousands of genes and putative regulatory elements with rapid-recall dynamics, shared and unique across the several memory populations. A core of memory-associated TFs (MAF, PRDM1, RUNX2, SMAD3 and KLF6) was predicted to orchestrate rapid recall and maintain accessible chromatin at rapid-recall gene enhancers in resting memory cells. KLF6 binding to its predicted target genes was confirmed by ChIP-seq, while the memory-associated activities of all five factors replicated in independent scRNA-seq studies. Using GWAS to link our T cell populations and their dynamic chromatin landscapes to human phenotypes, we nominate CD4+ T cell populations, rapid recall responses and gene regulatory mechanisms that might mediate genetic risk to autoimmune and inflammatory diseases.
2026-01-05 | GSE282266 | GEO
Project description:Gene regulatory network determinants of rapid recall in human memory T cells
| PRJNA1188017 | ENA
Project description:During T cell responses, a fraction of activated cells adopts a memory phenotype and returns to quiescence. These long-lived memory T cells retain an irreversible molecular imprint that enables them to mount a secondary recall response to the same antigen that is faster and greater in magnitude than the primary response of a naive cell. Memory T cells provide long-lasting immunological protection, forming the foundation for vaccination strategies and representing prime targets for immunotherapies to treat diseases characterized by dysfunctional memory T cells - including cancer and chronic inflammation. The molecular circuitry that endows memory T cells with their rapid recall ability remains incompletely understood. Here, we applied a multi-layered 1D-3D epigenomics approach to systematically dissect the molecular program driving rapid recall in primary human Th2 cells.
2023-07-24 | GSE207738 | GEO
Project description:Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate. How memory T cells efficiently ‘recall’ an inflammatory transcriptional program remains unclear. Here, we show that primary human CD4+ memory T helper (Th) cells carry three distinct activation-inducible recall gene modules that drive metabolic adaptation, T cell activation and inflammatory cytokine production. Enhancer elements controlling recall genes were epigenetically primed through the local maintenance of transcription-permissive chromatin in resting memory Th cells. At the three-dimensional level, recall genes clustered in transcriptionally permissive subnuclear compartments and resided in topologically associating domains (‘memory TADs’), in which activation-associated promoter-enhancer interactions were pre-formed. This primed epigenomic landscape was exploited by AP-1 transcription factors - including MAF - to promote rapid transcriptional activation. Finally, recall genes and their enhancers were linked to memory Th cell dysfunction in chronic inflammatory disease. Together, our results implicate multi-scale epigenomic priming - comprising a specialized three-dimensional chromatin organization - as a key mechanism underlying immunological memory.
2023-08-08 | GSE211023 | GEO
Project description:Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate. How memory T cells efficiently ‘recall’ an inflammatory transcriptional program remains unclear. Here, we show that primary human CD4+ memory T helper (Th) cells carry three distinct activation-inducible recall gene modules that drive metabolic adaptation, T cell activation and inflammatory cytokine production. Enhancer elements controlling recall genes were epigenetically primed through the local maintenance of transcription-permissive chromatin in resting memory Th cells. At the three-dimensional level, recall genes clustered in transcriptionally permissive subnuclear compartments and resided in topologically associating domains (‘memory TADs’), in which activation-associated promoter-enhancer interactions were pre-formed. This primed epigenomic landscape was exploited by AP-1 transcription factors - including MAF - to promote rapid transcriptional activation. Finally, recall genes and their enhancers were linked to memory Th cell dysfunction in chronic inflammatory disease. Together, our results implicate multi-scale epigenomic priming - comprising a specialized three-dimensional chromatin organization - as a key mechanism underlying immunological memory.
2023-08-08 | GSE210958 | GEO
Project description:Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the naïve cells. The mechanisms behind this rapid recall response of the memory cells are still not completely understood. Here, we performed epigenetic profiling of human resting naïve, central and effector memory T cells using ChIP-Seq and found that unlike the naïve cells, the regulatory elements of the cytokine genes in the memory T cells are marked by activating histone modifications even in the resting state. Therefore, the ability to induce expression of rapid recall genes upon activation is associated with the deposition of positive histone modifications during memory T cell differentiation. We propose a model of T cell memory, in which immunological memory state is encoded epigenetically, through poising and transcriptional memory.
2017-01-10 | GSE89404 | GEO
Project description:The physical manifestations of memory formation and recall are fundamental questions that remain unresolved. At the cellular level, ensembles of neurons called engrams are activated by learning events and control memory recall. Astrocytes are in close proximity to neurons and engage in a range of activities that support neurotransmission and circuit plasticity. Moreover, astrocytes exhibit experience dependent plasticity; however whether specific ensembles of astrocytes participate in memory recall remains obscure. Here we show that learning events induce c-Fos expression in a subset of hippocampal astrocytes, which subsequently regulates hippocampal circuit function. Intersectional, c-Fos based labeling of these astrocyte ensembles after learning events reveals that they are closely affiliated with engram neurons, while re-activation of these astrocyte ensembles stimulates memory recall. At the molecular level, these astrocyte ensembles exhibit elevated expression of NFIA and its selective deletion from this population suppresses memory recall. Together, our studies identify learning-associated astrocyte ensembles as a new form of plasticity that is sufficient to provoke memory recall, while implicating astrocytes as a reservoir for the storage of memories.
2024-06-30 | GSE254016 | GEO
Project description:The data contained in this Experiment come from 10X Chromium Genomics WGS of HepG2 cell line For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-06-15 | GSE177129 | GEO
Project description:The library contained in this Experiment corresponds to 10X Genomics Chromium prepared WGS. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf
2021-06-15 | GSE177554 | GEO