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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [DNA-seq]

ABSTRACT: TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [DNA-seq]

PROVIDER: PRJNA867426 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20973500_1.fastq.gz	Fastqsanger.gz
	SRR20973500_2.fastq.gz	Fastqsanger.gz
	SRR20973600_1.fastq.gz	Fastqsanger.gz
	SRR20973600_2.fastq.gz	Fastqsanger.gz
	SRR20973700_1.fastq.gz	Fastqsanger.gz

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [scMULT]

Project description:Coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. Emerging evidence points towards an important role of preexisting host factors, such as a deregulated inflammatory response at the time of infection. Here, we demonstrate the negative impact of clonal hematopoiesis, a prevalent clonal disorder of ageing individuals, on COVID-19-related cytokine release severity and mortality. In this study we perform Multiome single cell sequencing of PBMCs from COVID19 patients and patients with clonal hematopoiesis.

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [scRNA-seq]

Project description:Coronavirus disease 2019 (COVID-19) is associated with significant morbidity and mortality, albeit with considerable heterogeneity among affected individuals. Emerging evidence points towards an important role of preexisting host factors, such as a deregulated inflammatory response at the time of infection. Here, we demonstrate the negative impact of clonal hematopoiesis, a prevalent clonal disorder of ageing individuals, on COVID-19-related cytokine release severity and mortality. In this study we perform single cell RNA sequencing of PBMCs from COVID19 patients and patients with clonal hematopoiesis.

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality

Project description:TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality.

Project description:TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality.

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [scMULT]

Project description:TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [scMULT]

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [scRNA-seq]

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality

Project description:In this study we performed single-cell DNAseq + proteogenomics of PBMCs from COVID19 patients and patients with clonal hematopoiesis to identify the cell types that carry the mutations of interest.

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TET2 Mutant Clonal Hematopoiesis Enhances Severity of COVID-19 Related Cytokine Release Syndrome and is Associated with Increased Mortality [DNA-seq]

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Tet2-mediated clonal hematopoiesis in nonconditioned mice accelerates age-associated cardiac dysfunction

Project description:Clonal hematopoiesis of indeterminate potential is prevalent in elderly individuals and associated with increased risks of all-cause mortality and cardiovascular disease. However, mouse models to study the dynamics of clonal hematopoiesis and its consequences on the cardiovascular system under homeostatic conditions are lacking. We used a model of clonal hematopoiesis using adoptive transfer of unfractionated ten-eleven translocation 2-mutant (Tet2-mutant) bone marrow cells into nonirradiated mice. Consistent with age-related clonal hematopoiesis observed in humans, these mice displayed a progressive expansion of Tet2-deficient cells in multiple hematopoietic stem and progenitor cell fractions and blood cell lineages. The expansion of the Tet2-mutant fraction was also observed in bone marrow-derived CCR+ myeloid cell populations within the heart, but there was a negligible impact on the yolk sac-derived CCR2- cardiac resident macrophage population. Transcriptome profiling revealed an enhanced inflammatory signature in the donor-derived macrophages isolated from the heart. Mice receiving Tet2-deficient bone marrow cells spontaneously developed age-related cardiac dysfunction characterized by greater hypertrophy and fibrosis. Altogether, we show that Tet2- mediated hematopoiesis contributes to cardiac dysfunction in a nonconditioned setting that faithfully models the human clonal hematopoiesis in unperturbed bone marrow. Our data support clinical findings that clonal hematopoiesis per se may contribute to diminished health span.

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