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 (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Barmada, Anis (University of Cambridge. Department of Medical Genetics)
Morante-Palacios, Octavio (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
de la Calle-Fabregat, Carlos (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martins-Ferreira, Ricardo (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ferreté-Bonastre, Anna G. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ciudad, Laura (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Ruiz-Sanmartín, Adolfo (Universitat Autònoma de Barcelona. Departament de Medicina)
Martínez Gallo, Mónica (Hospital Universitari Vall d'Hebron)
Ferrer, Ricard (Universitat Autònoma de Barcelona. Departament de Medicina)
Ruiz-Rodriguez, Juan Carlos (Universitat Autònoma de Barcelona. Departament de Medicina)
Rodríguez-Ubreva, Javier (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Vento-Tormo, Roser (Wellcome Sanger Institute. Wellcome Genome Campus, Hinxton, UK)
Ballestar, Esteban (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)

Fecha:	2022
Resumen:	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. 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. 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. 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. The online version contains supplementary material available at 10. 1186/s13073-022-01137-4.
Ayudas:	Agencia Estatal de Investigación PID2020-117212RB-I00 Instituto de Salud Carlos III PI18/00346
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	COVID-19 ; Monocytes ; Epigenomics ; DNA methylation ; Single-cell transcriptomics ; Immune cell crosstalk
Publicado en:	Genome Medicine, Vol. 14 (november 2022) , ISSN 1756-994X

DOI: 10.1186/s13073-022-01137-4
PMID: 36443794

22 p, 5.6 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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