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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1415317
This article is part of the Research Topic Deciphering the Intricate Relationship between Epigenetics and Transcription in Immune System Regulation View all 4 articles
Remodeling of the chromatin landscape in peripheral blood cells in patients with severe Delta COVID-19
Provisionally accepted- 1 Centre for Strategic Planning, Moscow, Moscow Oblast, Russia
- 2 Federal Medical & Biological Agency of Russia, Moscow, Moscow Oblast, Russia
COVID-19 is characterized by systemic proinflammatory shifts with development of serious alterations in the functioning of the immune system. Investigations of the gene expression changes accompanying infection state provide insight towards standing of the molecular and cellular processes depending on the sickness severity and virus variant. Severe Delta COVID-19 have been characterized by the appearance of the monocyte subset enriched for the proinflammatory gene expression signatures and shift of the ligand-receptor interactions. We profiled the chromatin accessibility landscape of 140,000 nuclei of the PBMC samples from healthy people or individuals with COVID-19. We investigated cis-regulatory elements and identified core transcription factors governing the gene expression state 1 in immune cells during COVID-19. For the severe cases we discovered that regulome and chromatin co-accessibility modules significantly altered across many cell types. Moreover, cases with the Delta variant are accompanied by specific monocyte subtype discovered with the scATAC-seq data. From our analysis follows that immune cells of individuals with severe Delta COVID-19 undergo significant remodeling of the chromatin accessibility landscape and development of the proinflammatory expression pattern. With a gene regulatory network modeling approach we investigated core transcription factors governing cell state and identified the most pronounced chromatin changes in CD14+ monocytes from individuals with severe Delta COVID-19. Together, our results provide novel insight into the cis-regulatory module organization and their impact on gene activity in immune cells during SARS-CoV-2 infection.
Keywords: scATAC-seq, single cell, COVID-19, Transcriptional regularoty network, PBMC (peripheral blood mononuclear cells)
Received: 10 Apr 2024; Accepted: 20 Aug 2024.
Copyright: © 2024 Akimov, Tychinin, Antonova, Shaymardanov, Voronina, Deinichenko, Fateev, Yudin, Yudin, Mukhin, Romanova, Akinshina, Zhdanova, Tsypkina, Makhotenko, Keskinov, Kraevoy, Snigir, Svetlichnyy and Skvortsova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Dmitry Svetlichnyy, Centre for Strategic Planning, Moscow, 119121, Moscow Oblast, Russia
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