Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity
Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity
Abstract SARS-CoV-2 infection triggers highly variable host responses and causes varying degrees of illness in humans. We sought to harness the peripheral blood mononuclear cell (PBMC) response over the course of illness to provide insight into COVID-19 physiology. We analyzed PBMCs from subjects with variable symptom severity at different stages of clinical illness before and after IgG seroconversion to SARS-CoV-2. Prior to seroconversion, PBMC transcriptomes did not distinguish symptom severity. In contrast, changes in chromatin accessibility were associated with symptom severity. Furthermore, single-cell analyses revealed evolution of the chromatin accessibility landscape and transcription factor motif occupancy for individual PBMC cell types. The most extensive remodeling occurred in CD14+ monocytes where sub-populations with distinct chromatin accessibility profiles were associated with disease severity. Our findings indicate that pre-seroconversion chromatin remodeling in certain innate immune populations is associated with divergence in symptom severity, and the identified transcription factors, regulatory elements, and downstream pathways provide potential prognostic markers for COVID-19 subjects. One sentence summaryChromatin accessibility in immune cells from COVID-19 subjects is remodeled prior to seroconversion to reflect disease severity.
Giroux Nicholas S.、Palomino Grecia R.、Ding Shengli、Kraft Bryan D.、Woods Christopher W.、Chung Hong A.、Bose Shree、Nicholson Bradly P.、Henao Ricardo、Sempowski Gregory D.、Denny Thomas N.、Shen Xiling、Ko Emily R.、Ginsburg Geoffrey S.、Wang Ergang、Chen Tianyi、McClain Micah T.、Xi Rui、Burke Thomas W.、Petzold Elizabeth、Rotstein Tomer、Tsalik Ephraim L.
Department of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University||Durham Veterans Affairs Health Care SystemCenter for Applied Genomics and Precision Medicine, Duke University||Durham Veterans Affairs Health Care System||Division of Infectious Diseases, Duke University Medical CenterDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Pharmacology and Cancer Biology, School of Medicine, Duke UniversityInstitute for Medical ResearchCenter for Applied Genomics and Precision Medicine, Duke UniversityDuke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke UniversityDuke Human Vaccine Institute and Department of Medicine, School of Medicine, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityDepartment of Molecular Genetics and Microbiology, School of Medicine, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University||Durham Veterans Affairs Health Care System||Division of Infectious Diseases, Duke University Medical CenterDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke UniversityDepartment of Biomedical Engineering, Pratt School of Engineering, Duke UniversityCenter for Applied Genomics and Precision Medicine, Duke University||Durham Veterans Affairs Health Care System||Division of Infectious Diseases, Duke University Medical Center
基础医学分子生物学生物科学研究方法、生物科学研究技术
Giroux Nicholas S.,Palomino Grecia R.,Ding Shengli,Kraft Bryan D.,Woods Christopher W.,Chung Hong A.,Bose Shree,Nicholson Bradly P.,Henao Ricardo,Sempowski Gregory D.,Denny Thomas N.,Shen Xiling,Ko Emily R.,Ginsburg Geoffrey S.,Wang Ergang,Chen Tianyi,McClain Micah T.,Xi Rui,Burke Thomas W.,Petzold Elizabeth,Rotstein Tomer,Tsalik Ephraim L..Chromatin remodeling in peripheral blood cells reflects COVID-19 symptom severity[EB/OL].(2025-03-28)[2025-04-26].https://www.biorxiv.org/content/10.1101/2020.12.04.412155.点此复制
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