Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines

COVID-19; Monocytes; Single-cell transcriptomics

Detalles Bibliográficos
Autores: Godoy-Tena, Gerard, Barmada, Anis, Morante-Palacios, Octavio, de la Calle-Fabregat, Carlos, Martins‑Ferreira, Ricardo, Ferrete-Bonastre, Anna G., Ruiz Sanmartin, Adolfo, Ferrer Roca, Ricard, Ruiz Rodriguez, Juan Carlos, Martínez Gallo, Mónica
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/8611
Acceso en línea:https://hdl.handle.net/11351/8611
http://hdl.handle.net/11351/8611
Access Level:acceso abierto
Palabra clave:COVID-19 (Malaltia)
Citocines
Epigènesi
DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic
CHEMICALS AND DRUGS::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::péptidos y proteínas de señalización intercelular::citocinas
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oai_identifier_str oai:recercat.cat:11351/8611
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
title Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
spellingShingle Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
Godoy-Tena, Gerard
COVID-19 (Malaltia)
Citocines
Epigènesi
DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic
CHEMICALS AND DRUGS::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::péptidos y proteínas de señalización intercelular::citocinas
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_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_sort Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines
dc.creator.none.fl_str_mv Godoy-Tena, Gerard
Barmada, Anis
Morante-Palacios, Octavio
de la Calle-Fabregat, Carlos
Martins‑Ferreira, Ricardo
Ferrete-Bonastre, Anna G.
Ruiz Sanmartin, Adolfo
Ferrer Roca, Ricard
Ruiz Rodriguez, Juan Carlos
Martínez Gallo, Mónica
author Godoy-Tena, Gerard
author_facet Godoy-Tena, Gerard
Barmada, Anis
Morante-Palacios, Octavio
de la Calle-Fabregat, Carlos
Martins‑Ferreira, Ricardo
Ferrete-Bonastre, Anna G.
Ruiz Sanmartin, Adolfo
Ferrer Roca, Ricard
Ruiz Rodriguez, Juan Carlos
Martínez Gallo, Mónica
author_role author
author2 Barmada, Anis
Morante-Palacios, Octavio
de la Calle-Fabregat, Carlos
Martins‑Ferreira, Ricardo
Ferrete-Bonastre, Anna G.
Ruiz Sanmartin, Adolfo
Ferrer Roca, Ricard
Ruiz Rodriguez, Juan Carlos
Martínez Gallo, Mónica
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Godoy-Tena G, Morante-Palacios O, de la Calle-Fabregat C, Martins-Ferreira R, Ferreté-Bonastre AG] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Barcelona, Spain. [Barmada A] Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Department of Medical Genetics, University of Cambridge, Cambridge, UK. [Ruiz-Sanmartín A, Ferrer R, Ruiz-Rodriguez JC] Servei de Medicina Intensiva, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Shock, Disfunció Orgànica i Ressuscitació, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Martínez-Gallo M] Servei d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv COVID-19 (Malaltia)
Citocines
Epigènesi
DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic
CHEMICALS AND DRUGS::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::péptidos y proteínas de señalización intercelular::citocinas
topic COVID-19 (Malaltia)
Citocines
Epigènesi
DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic
CHEMICALS AND DRUGS::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines
ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::péptidos y proteínas de señalización intercelular::citocinas
description COVID-19; Monocytes; Single-cell transcriptomics
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11351/8611
http://hdl.handle.net/11351/8611
url https://hdl.handle.net/11351/8611
http://hdl.handle.net/11351/8611
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genome Medicine;14
https://doi.org/10.1186/s13073-022-01137-4
info:eu-repo/grantAgreement/ES/PE2013-2016/PI18%2F00346
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMC
publisher.none.fl_str_mv BMC
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokinesGodoy-Tena, GerardBarmada, AnisMorante-Palacios, Octaviode la Calle-Fabregat, CarlosMartins‑Ferreira, RicardoFerrete-Bonastre, Anna G.Ruiz Sanmartin, AdolfoFerrer Roca, RicardRuiz Rodriguez, Juan CarlosMartínez Gallo, MónicaCOVID-19 (Malaltia)CitocinesEpigènesiDISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus InfectionsPHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, GeneticCHEMICALS AND DRUGS::Biological Factors::Intercellular Signaling Peptides and Proteins::CytokinesENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por CoronavirusFENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genéticaCOMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::péptidos y proteínas de señalización intercelular::citocinasCOVID-19; Monocytes; Single-cell transcriptomicsCOVID-19; Monocitos; Transcriptómica unicelularCOVID-19; Monòcits; Transcriptòmica unicel·lularBackground 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.This study has been funded by R+D+i project of the Spanish Ministry of Science and Innovation (grant number PID2020-117212RB-I00/ MICIN/AEI/10.13039/501100011033). We also thank the Chan Zuckerberg Initiative (grant 2020–216799) and Wellcome Sanger core funding (WT206194). This publication has also been supported by the Unstoppable campaign of the Josep Carreras Leukaemia Foundation. Additional funding comes from Project PI18/00346 (Instituto de Salud Carlos III and co-funded by European Union (ERDF/ESF ). A.B. received additional support from a Gates Cambridge Scholarship.BMCInstitut Català de la Salut[Godoy-Tena G, Morante-Palacios O, de la Calle-Fabregat C, Martins-Ferreira R, Ferreté-Bonastre AG] Epigenetics and Immune Disease Group, Josep Carreras Research Institute (IJC), Barcelona, Spain. [Barmada A] Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK. Department of Medical Genetics, University of Cambridge, Cambridge, UK. [Ruiz-Sanmartín A, Ferrer R, Ruiz-Rodriguez JC] Servei de Medicina Intensiva, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca de Shock, Disfunció Orgànica i Ressuscitació, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Martínez-Gallo M] Servei d’Immunologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Immunologia Diagnòstica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8611http://hdl.handle.net/11351/8611Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésGenome Medicine;14https://doi.org/10.1186/s13073-022-01137-4info:eu-repo/grantAgreement/ES/PE2013-2016/PI18%2F00346Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/86112026-05-29T05:05:01Z
score 15.198674

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