Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
Abstract Background COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about th...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-022-01137-4 |
| _version_ | 1811315272732114944 |
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| author | Gerard Godoy-Tena Anis Barmada Octavio Morante-Palacios Carlos de la Calle-Fabregat Ricardo Martins-Ferreira Anna G. Ferreté-Bonastre Laura Ciudad Adolfo Ruiz-Sanmartín Mónica Martínez-Gallo Ricard Ferrer Juan Carlos Ruiz-Rodriguez Javier Rodríguez-Ubreva Roser Vento-Tormo Esteban Ballestar |
| author_facet | Gerard Godoy-Tena Anis Barmada Octavio Morante-Palacios Carlos de la Calle-Fabregat Ricardo Martins-Ferreira Anna G. Ferreté-Bonastre Laura Ciudad Adolfo Ruiz-Sanmartín Mónica Martínez-Gallo Ricard Ferrer Juan Carlos Ruiz-Rodriguez Javier Rodríguez-Ubreva Roser Vento-Tormo Esteban Ballestar |
| author_sort | Gerard Godoy-Tena |
| collection | DOAJ |
| description | Abstract Background COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about the epigenetic alterations that occur in these cells during hyperinflammatory responses in severe COVID-19 patients. Methods In this study, we obtained the DNA methylome and transcriptome of peripheral blood monocytes from severe COVID-19 patients. DNA samples extracted from CD14 + CD15- monocytes of 48 severe COVID-19 patients and 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. In parallel, single-cell transcriptomics of 10 severe COVID-19 patients were generated. CellPhoneDB was used to infer changes in the crosstalk between monocytes and other immune cell types. Results We observed DNA methylation changes in CpG sites associated with interferon-related genes and genes associated with antigen presentation, concordant with gene expression changes. These changes significantly overlapped with those occurring in bacterial sepsis, although specific DNA methylation alterations in genes specific to viral infection were also identified. We also found these alterations to comprise some of the DNA methylation changes occurring during myeloid differentiation and under the influence of inflammatory cytokines. A progression of DNA methylation alterations in relation to the Sequential Organ Failure Assessment (SOFA) score was found to be related to interferon-related genes and T-helper 1 cell cytokine production. CellPhoneDB analysis of the single-cell transcriptomes of other immune cell types suggested the existence of altered crosstalk between monocytes and other cell types like NK cells and regulatory T cells. Conclusion Our findings show the occurrence of an epigenetic and transcriptional reprogramming of peripheral blood monocytes, which could be associated with the release of aberrant immature monocytes, increased systemic levels of pro-inflammatory cytokines, and changes in immune cell crosstalk in these patients. |
| first_indexed | 2024-04-13T11:27:19Z |
| format | Article |
| id | doaj.art-3b4819c3d77f43b3ba8de2a54e094d11 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-13T11:27:19Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-3b4819c3d77f43b3ba8de2a54e094d112022-12-22T02:48:39ZengBMCGenome Medicine1756-994X2022-11-0114112210.1186/s13073-022-01137-4Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokinesGerard Godoy-Tena0Anis Barmada1Octavio Morante-Palacios2Carlos de la Calle-Fabregat3Ricardo Martins-Ferreira4Anna G. Ferreté-Bonastre5Laura Ciudad6Adolfo Ruiz-Sanmartín7Mónica Martínez-Gallo8Ricard Ferrer9Juan Carlos Ruiz-Rodriguez10Javier Rodríguez-Ubreva11Roser Vento-Tormo12Esteban Ballestar13Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Wellcome Sanger Institute, Wellcome Genome CampusEpigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Intensive Care Department, Vall d’Hebron University Hospital, Shock, Organ Dysfunction and Resuscitation (SODIR) Research Group, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaImmunology Division, Vall d’Hebron University Hospital and Diagnostic Immunology Research Group, Vall d’Hebron Research Institute (VHIR)Intensive Care Department, Vall d’Hebron University Hospital, Shock, Organ Dysfunction and Resuscitation (SODIR) Research Group, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaIntensive Care Department, Vall d’Hebron University Hospital, Shock, Organ Dysfunction and Resuscitation (SODIR) Research Group, Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de BarcelonaEpigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Wellcome Sanger Institute, Wellcome Genome CampusEpigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC)Abstract Background COVID-19 manifests with a wide spectrum of clinical phenotypes, ranging from asymptomatic and mild to severe and critical. Severe and critical COVID-19 patients are characterized by marked changes in the myeloid compartment, especially monocytes. However, little is known about the epigenetic alterations that occur in these cells during hyperinflammatory responses in severe COVID-19 patients. Methods In this study, we obtained the DNA methylome and transcriptome of peripheral blood monocytes from severe COVID-19 patients. DNA samples extracted from CD14 + CD15- monocytes of 48 severe COVID-19 patients and 11 healthy controls were hybridized on MethylationEPIC BeadChip arrays. In parallel, single-cell transcriptomics of 10 severe COVID-19 patients were generated. CellPhoneDB was used to infer changes in the crosstalk between monocytes and other immune cell types. Results We observed DNA methylation changes in CpG sites associated with interferon-related genes and genes associated with antigen presentation, concordant with gene expression changes. These changes significantly overlapped with those occurring in bacterial sepsis, although specific DNA methylation alterations in genes specific to viral infection were also identified. We also found these alterations to comprise some of the DNA methylation changes occurring during myeloid differentiation and under the influence of inflammatory cytokines. A progression of DNA methylation alterations in relation to the Sequential Organ Failure Assessment (SOFA) score was found to be related to interferon-related genes and T-helper 1 cell cytokine production. CellPhoneDB analysis of the single-cell transcriptomes of other immune cell types suggested the existence of altered crosstalk between monocytes and other cell types like NK cells and regulatory T cells. Conclusion Our findings show the occurrence of an epigenetic and transcriptional reprogramming of peripheral blood monocytes, which could be associated with the release of aberrant immature monocytes, increased systemic levels of pro-inflammatory cytokines, and changes in immune cell crosstalk in these patients.https://doi.org/10.1186/s13073-022-01137-4COVID-19MonocytesEpigenomicsDNA methylationSingle-cell transcriptomicsImmune cell crosstalk |
| spellingShingle | Gerard Godoy-Tena Anis Barmada Octavio Morante-Palacios Carlos de la Calle-Fabregat Ricardo Martins-Ferreira Anna G. Ferreté-Bonastre Laura Ciudad Adolfo Ruiz-Sanmartín Mónica Martínez-Gallo Ricard Ferrer Juan Carlos Ruiz-Rodriguez Javier Rodríguez-Ubreva Roser Vento-Tormo Esteban Ballestar Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines Genome Medicine COVID-19 Monocytes Epigenomics DNA methylation Single-cell transcriptomics Immune cell crosstalk |
| title | Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| title_full | Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| title_fullStr | Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| title_full_unstemmed | Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| title_short | Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| title_sort | epigenetic and transcriptomic reprogramming in monocytes of severe covid 19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines |
| topic | COVID-19 Monocytes Epigenomics DNA methylation Single-cell transcriptomics Immune cell crosstalk |
| url | https://doi.org/10.1186/s13073-022-01137-4 |
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