ArticleProceedings of the National Academy of Sciences of the United States of America2021
E2A-regulated epigenetic landscape promotes memory CD8 T cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Nonoxidative pentose phosphate pathway regulates CD8Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A prevalent disease-associated SNP in the humanNAR molecular medicine · 2026Article
- Mechanisms of T cell activation: Integrating signaling pathways, experimental models, and therapeutic implications.EXCLI journal · 2026Review
- From exhaustion to functional cure: frontiers in reversing HBV-specific T-cell immunity.Frontiers in immunology · 2026Review
- Article
- CCR2Cellular & molecular immunology · 2025Article
- UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.Life science alliance · 2025Article
- Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression.Science immunology · 2025Article
- HEB Restrains Effector Gene Expression during Early CD8Molecular and cellular biology · 2025Article
- Histone lactylation drives CD8Nature immunology · 2024Article
- Sustained AhR activity programs memory fate of early effector CD8Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Memory B cell subsets have divergent developmental origins that are coupled to distinct imprinted epigenetic states.Nature immunology · 2024Article
- ADGRE5-centered Tsurv model in T cells recognizes responders to neoadjuvant cancer immunotherapy.Frontiers in immunology · 2024Article
- A spatial sequencing atlas of age-induced changes in the lung during influenza infection.Nature communications · 2023Article
- Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia.BMC genomics · 2023Observational
- Regulation and Immunotherapeutic Targeting of the Epigenome in Exhausted CD8 T Cell Responses.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Autoreactive CD8 T cells in NOD mice exhibit phenotypic heterogeneity but restricted TCR gene usage.Life science alliance · 2022Article
- Article
- Metabolic alterations impair differentiation and effector functions of CD8+ T cells.Frontiers in immunology · 2022Article
- Signaling networks controlling ID and E protein activity in T cell differentiation and function.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
During an acute viral infection, CD8 T cells encounter a myriad of antigenic and inflammatory signals of variable strength, which sets off individual T cells on their own differentiation trajectories. However, the developmental path for each of these cells will ultimately lead to one of only two potential outcomes after clearance of the infection-death or survival and development into memory CD8 T cells. How this cell fate decision is made remains incompletely understood. In this study, we explore the transcriptional changes during effector and memory CD8 T cell differentiation at the single-cell level. Using single-cell, transcriptome-derived gene regulatory network analysis, we identified two main groups of regulons that govern this differentiation process. These regulons function in concert with changes in the enhancer landscape to confer the establishment of the regulatory modules underlying the cell fate decision of CD8 T cells. Furthermore, we found that memory precursor effector cells maintain chromatin accessibility at enhancers for key memory-related genes and that these enhancers are highly enriched for E2A binding sites. Finally, we show that E2A directly regulates accessibility of enhancers of many memory-related genes and that its overexpression increases the frequency of memory precursor effector cells and accelerates memory cell formation while decreasing the frequency of short-lived effector cells. Overall, our results suggest that effector and memory CD8 T cell differentiation is largely regulated by two transcriptional circuits, with E2A serving as an important epigenetic regulator of the memory circuit.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.