The DOI matches its Crossref record; 69 of the 70 references it cites were found in a registry or an index.
Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity
Open accessAbstract
Monocyte differentiation into macrophages represents a cornerstone process for host defense. Concomitantly, immunological imprinting of either tolerance or trained immunity determines the functional fate of macrophages and susceptibility to secondary infections. We characterized the transcriptomes and epigenomes in four primary cell types: monocytes and in vitro-differentiated naïve, tolerized, and trained macrophages. Inflammatory and metabolic pathways were modulated in macrophages, including decreased inflammasome activation, and we identified pathways functionally implicated in trained immunity. β-glucan training elicits an exclusive epigenetic signature, revealing a complex network of enhancers and promoters. Analysis of transcription factor motifs in deoxyribonuclease I hypersensitive sites at cell-type-specific epigenetic loci unveiled differentiation and treatment-specific repertoires. Altogether, we provide a resource to understand the epigenetic changes that underlie innate immunity in humans.
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“The same modifications of histone 3 were present in immune relevant gene locations in myeloid cells of humans and mice after induction of trained immunity [8,9,40].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [9]
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“Beta glucan exposure can induce these modifications in mammals, via the dectin-1 receptor [7,8,9].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [9]
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“Trained immunity in mice results from epigenetic reprogramming of monocytes and macrophages through acetylation or methylation of specific lysines in the histone-H3 [8,9].”
From Trained Immunity Provides Long-Term Protection against Bacterial Infections in Channel Catfish (2022) · cites this paper as [9]
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“PCA of our human microglial and published monocyte and macrophage data 30 indicated that these three data sets segregated and that microglia were the most distinct ( Supplementary Figure 1a ).”
From Transcriptomic analysis of purified human cortical microglia reveals age-associated changes (2017) · cites this paper as [30]
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Cites
Macrophage plasticity and polarization: in vivo veritas
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Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684
Development of Monocytes, Macrophages, and Dendritic Cells
Geissmann, F., Manz, M. G., Jung, S., Sieweke, M. H., Merad, M., & Ley, K. (2010) · Science · doi:10.1126/science.1178331 · Cited by 3,049
The accessible chromatin landscape of the human genome
Thurman, R. E., Rynes, E., Humbert, R., Vierstra, J., Maurano, M. T., Haugen, E., Sheffield, N. C., Stergachis, A. B., Wang, H., Vernot, B., et al. (2012) · Nature · doi:10.1038/nature11232 · Cited by 2,679
Regulation and Function of NF-κB Transcription Factors in the Immune System
Vallabhapurapu, S., & Karin, M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132641 · Cited by 2,635
Histone modifications at human enhancers reflect global cell-type-specific gene expression
Heintzman, N. D., Hon, G. C., Hawkins, R. D., Kheradpour, P., Stark, A., Harp, L. F., Ye, Z., Lee, L. K., Stuart, R. K., Ching, C. W., et al. (2009) · Nature · doi:10.1038/nature07829 · Cited by 2,533
Martínez, F. O., Gordon, S., Locati, M., & Mantovani, A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.10.7303 · Cited by 2,399
A unique chromatin signature uncovers early developmental enhancers in humans
Rada-Iglesias, A., Bajpai, R., Swigut, T., Brugmann, S. A., Flynn, R. A., & Wysocka, J. (2011) · Nature · doi:10.1038/nature09692 · Cited by 2,233
mTOR- and HIF-1α–mediated aerobic glycolysis as metabolic basis for trained immunity
Cheng, S.-C., Quintin, J., Cramer, R. A., Shepardson, K. M., Saeed, S., Kumar, V., Giamarellos-Bourboulis, E. J., Martens, J. H. A., Rao, N. A., Aghajanirefah, A., et al. (2014) · Science · doi:10.1126/science.1250684 · Cited by 2,224
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Sanchez Vasquez, J. D., Nkongolo, S., Traum, D., Sotov, V., Kim, S. C., Mahamed, D., Mehrotra, A., Patel, A., Chen, D. Y., Fung, S., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci175241 · Cited by 11
Microglial states revisited: from homeostasis to disease
Eggen, B. J. L., & Kooistra, S. M. (2026) · Nature Reviews Neuroscience · doi:10.1038/s41583-026-01066-w · Cited by 6
Type 1 interferon perturbates clonal competition by reshaping human blood development
Lama, C., Isakov, D., Rosenberg, S., Quijada-Álamo, M., Saurty-Seerunghen, M. S., Moein, S., Nozais, M., Abera, T.-A., Sakaguchi, O., Totwani, M., et al. (2026) · Nature Genetics · doi:10.1038/s41588-026-02751-3 · Cited by 3
Metadata
- Authors
- Saeed, S., Quintin, J., Kerstens, H. H. D., Rao, N. A., Aghajanirefah, A., Matarese, F., Cheng, S.-C., Ratter, J., Berentsen, K., van der Ent, M. A., Sharifi, N., Janssen-Megens, E. M., Ter Huurne, M., Mandoli, A., van Schaik, T., Ng, A., Burden, F., Downes, K., Frontini, M., Kumar, V., Giamarellos-Bourboulis, E. J., Ouwehand, W. H., van der Meer, J. W. M., Joosten, L. A. B., Wijmenga, C., Martens, J. H. A., Xavier, R. J., Logie, C., Netea, M. G., & Stunnenberg, H. G.
- Affiliations
- Radboud University Nijmegen (NL)
- Radboud University Medical Center (NL)
- Department of Molecular Biology, Faculties of Science and Medicine, Radboud Institute for Molecular Life Sciences, Radboud University, 6500 HB Nijmegen, Netherlands.
- Broad Institute (US)
- National Health Service (GB)
- University Medical Center Groningen (NL)
- Fourth Department of Internal Medicine, University of Athens, Medical School, 1 Rimini Street, 12462 Athens, Greece.
- Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
- Corresponding author
- Saeed, Sadia
- Quintin, Jessica
- Kerstens, Hindrik H. D.
- Rao, Nagesha A.
- Aghajanirefah, Ali
- Logie, Colin
- Netea, Mihai G.
- Stunnenberg, Hendrik G.
- ORCID
- Venue
- Science
- Published
- 2014-09-26
- Volume
- 345
- Issue
- 6204
- Pages
- 1251086-1251086
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4242194
- OpenAlex
- W2140876277
- Cited by
- 1,761
- References
- 70
- Citations by year
- 2026: 197 · 2025: 162 · 2024: 143 · 2023: 150 · 2022: 174 · 2021: 184 · 2020: 168 · 2019: 134 · 2018: 129 · 2017: 114 · 2016: 120 · 2015: 76 · 2014: 9
- FWCI
- 48.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institute for Health and Care Research (NF-SI-0510-10214, RP-PG-0310-1002, NF-SI-0513-10151)
- British Heart Foundation (RG/09/012/28096)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- monocyte-to-macrophage differentiation, trained immunity, immunological imprinting, epigenetic programming, macrophage transcriptome, inflammasome activation, transcription factor binding motifs, innate immunity
- MeSH terms
- Animals, Binding Sites, Cell Differentiation, Deoxyribonuclease I, Humans, Immunity, Innate, Immunologic Memory, Macrophages, Monocytes, Transcription Factors, Genomic Imprinting, Epigenesis, Genetic, beta-Glucans, Mice, Inflammasomes
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