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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210435 | GEO | 2024/08/13

REPOSITORIES: GEO

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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.

2024-08-14 | GSE211379 | GEO

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.

2024-08-14 | GSE210432 | GEO

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

Project description:In this study we performed DNA Sequencing of PBMCs to identify mutations associated with clonal hematopoiesis in patients with COVID19 and non-COVID19 patients.

2024-08-14 | GSE210782 | GEO

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.

2024-08-14 | GSE210433 | GEO

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.

| PRJNA865718 | ENA

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]

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

| PRJNA865721 | ENA

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

Project description: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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Aging drives Tet2+/- clonal hematopoiesis via IL-1 signaling.

Project description:Clonal hematopoiesis of indeterminate potential (CHIP), also referred to as aging-related clonal hematopoiesis, is defined as an asymptomatic clonal expansion of mutant mature hematopoietic cells in ≥4% of blood leukocytes. CHIP associates with advanced age and increased risk for hematological malignancy, cardiovascular disease, and all-cause mortality. Loss-of-function somatic mutations in TET2 are frequent drivers of CHIP. However, the contribution of aging-associated cooperating cell-extrinsic drivers, like inflammation, remains underexplored. Using bone marrow (BM) transplantation and newly developed genetic mosaicism (HSC-SCL-Cre-ERT; Tet2+/flox; R26+/tm6[CAG-ZsGreen1]Hze) mouse models of Tet2+/-driven CHIP, we observed an association between increased Tet2+/- clonal expansion and higher BM levels of the inflammatory cytokine interleukin-1 (IL-1) upon aging. Administration of IL-1 to mice carrying CHIP led to an IL-1 receptor 1 (IL-1R1)-dependent expansion of Tet2+/- hematopoietic stem and progenitor cells (HSPCs) and mature blood cells. This expansion was caused by increased Tet2+/- HSPC cell cycle progression, increased multilineage differentiation, and higher repopulation capacity compared with their wild-type counterparts. In agreement, IL-1α-treated Tet2+/- hematopoietic stem cells showed increased DNA replication and repair transcriptomic signatures and reduced susceptibility to IL-1α-mediated downregulation of self-renewal genes. More important, genetic deletion of IL-1R1 in Tet2+/- HPSCs or pharmacologic inhibition of IL-1 signaling impaired Tet2+/- clonal expansion, establishing the IL-1 pathway as a relevant and therapeutically targetable driver of Tet2+/- CHIP progression during aging.

| S-EPMC10651783 | biostudies-literature