Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ATACSeq of TET2-mutant human neutrophils

ABSTRACT: Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE213768 | GEO | 2023/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RRBS of TET2-mutant human neutrophils

Project description:Somatic mutations acquired by hematopoietic stem cells (HSCs) are commonly found over the course of a lifespan. Some of these clones will outgrow through a process known as clonal hematopoiesis (CH) and produce mutated immune cell progeny, which will shape host immunity. Individuals with CH are asymptomatic but have increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Despite the key role that neutrophils play in the development of such diseases, little is known about how these prevalent somatic mutations affect neutrophil functionality. In this work, we describe how mutations in TET2, one of the most common mutated genes in individuals with CH, affect human neutrophil biology.

2023-12-01 | GSE213770 | GEO

RNASeq of TET2-mutant human neutrophils

2023-12-01 | GSE213769 | GEO

RNASeq of TET2-mutant human neutrophils

2023-06-05 | GSE228077 | GEO

Single-cell multi-omics in human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation.

Project description:Clonal hematopoiesis (CH) reflects clonal expansion of blood stem and progenitor cells with somatic mutations. We leveraged multi-modality single-cell sequencing to capture mutation status together with the transcriptome and methylome of CD34+ hematopoietic progenitor cells from five individuals with DNMT3A R882-mutated CH.

2022-07-05 | GSE158067 | GEO

Selection Pressures in the Aged Microenvironment Drive Transformation of Dnmt3a-Mutant Hematopoietic Stem Cells to Myeloid Malignancy

Project description:Driver somatic mutations in adult acute myeloid leukemia (AML) are often preceded by a benign or premalignant state termed clonal hematopoiesis (CH) for which the greatest risk factor is aging. To risk-stratify aged individuals and develop therapies to prevent AML, we need to understand the variables that promote transformation from CH to AML. Using our orthogonally inducible Dnmt3aR878H;Npm1cA-mutant model of progression from CH to myeloid malignancy, we find that in young mice, Dnmt3a mutation buffers against myeloid differentiation, proliferation, acquisition of cooperating mutations and transformation induced by stress, inflammation, and the oncogenic Npm1 mutation. However, when Dnmt3a;Npm1-mutant hematopoietic stem cells (HSCs) are transplanted into naturally aged recipient mice, they gain myeloid-biased differentiation capacity and have an accelerated transformation to AML. These results support the hypothesis that alterations in the aged microenvironment drive risk of AML in individuals with CH and help to explain why this Dnmt3a mutation is exceedingly rare in pediatric leukemias.

2021-07-15 | GSE180116 | GEO

RNA seq analysis of calcium channel blocker, nifedipine in combination with metformin, MCC950 and anakinra treated Tet2-/- + Boy/J (1:1 ratio, mixed BM cells) transplanted Ob/Ob recipient mice

Project description:Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis (CH) of indeterminate potential (CHIP) involves expansion of mutated hematopoietic stem and progenitor cells (HSC/Ps) that leads to an increased risk of hematologic malignancy and cardiovascular disease (CVD). However, risk factors that contribute to CHIP-associated CH are poorly understood. A common, pro-inflammatory comorbidity responsible for enhancing the risk for developing type 2 diabetes mellitus (T2DM), CVD and cancer, obesity may exacerbate CHIP-associated diseases. We analyzed exome sequencing and clinical data from 47,466 individuals with valid CHIP in the UK Biobank. CHIP was present in 5.8% of the study population, and was associated with a significant increase in waist-to-hip ratio (WHR). The cancer genome atlas (TCGA) interrogation revealed that the mutation rate of CHIP is higher in patients with high BMI (>30 kg/m2) compared to those with low BMI (≤25 kg/m2) in six different cancer types. Utilizing mouse models of obesity bearing CHIP mutations, we show that both the compound mutant mice (Tet2-/-;Ob/Ob, Dnmt3a+/-;Ob/Ob) and CHIP mutant bone marrow (BM; Tet2-/-, Dnmt3a+/-, Asxl1+/- and Jak2+/-) transplanted into Ob/Ob mice develop rapid CH, leading to severe MPN/AML as well as CVD, which among other things, is associated with upregulation of intracellular calcium (Ca2+) levels and pro-inflammatory cytokines. Remarkably, calcium channel blocker nifedipine, in combination with metformin, MCC950 and anakinra, suppressed the growth of mutant CHIP cells, cardiovascular disease and restored normal hematopoiesis as well as serum Ca2+ and inflammatory cytokines. Thus, obesity is highly associated with the presence of CHIP and targeting CHIP mutant cells with a combination of metformin/nifedipine/MCC950/anakinra is a safe and inexpensive approach to treat CH and its associated abnormalities in obese individuals.

2022-01-08 | GSE193062 | GEO

TP53-mediated therapy-related clonal hematopoiesis contributes to doxorubicin-induced cardiomyopathy by augmenting a neutrophil-mediated cytotoxic response in a murine model

Project description:Therapy-related clonal hematopoiesis (t-CH) is often observed in cancer survivors. This form of clonal hematopoiesis typically involves somatic mutations in driver genes that encode components of the DNA damage response (DDR) and confer hematopoietic stem and progenitor cells (HSPC) with resistance to the genotoxic stress of the cancer therapy. A model of TP53-mediated t-CH was established through the transfer of Trp53-mutant HSPC to mice followed by treatment with a course of the chemotherapeutic agent doxorubicin. These studies revealed that neutrophil infiltration in the heart significantly contributes to doxorubicin-induced cardiac toxicity and that this condition is amplified in the model of Trp53-mediated t-CH. These data suggest t-CH could contribute to the elevated heart failure risk that occurs in cancer survivors.

2021-05-05 | GSE173840 | GEO

Clonal Haematopoiesis-related Mutant ASXL1 Promotes Atherosclerosis in Mice via Dysregulated Innate Immunity

Project description:Certain somatic mutations confer a fitness advantage in hematopoietic stem cells, resulting in the clonal expansion of mutant blood cells, known as clonal haematopoiesis (CH). Among the top 3 CH mutations, ASXL1 mutations present the highest risk for developing cardiovascular diseases (CVDs). However, how ASXL1 mutations induce CVDs remains totally elusive. Here we show that haematopoietic cells harbouring C-terminally truncated form of ASXL1 mutant (ASXL1-MT) accelerated development of atherosclerosis in Ldlr–/– mice. Transcriptome analyses of plaque-cells showed inflammatory signatures of monocytes and macrophages expressing ASXL1-MT. Mechanistically, wild-type ASXL1 inhibited innate immune signalling through the inhibition of IRAK1-TAK1 interaction in the cytoplasm, indicating an unexpected non-epigenetic role of ASXL1. In contrast, ASXL1-MT lost this regulatory function, leading to NF-κB activation. Intriguingly, IRAK1/4 inhibition decreased inflammatory monocytes and atherosclerosis driven by ASXL1-MT. The present work connects ASXL1 mutations with inflammation and CVDs, giving a clue to prevent CVDs in ASXL1-CH.

2024-10-25 | GSE279450 | GEO

Clonal Haematopoiesis-related Mutant ASXL1 Promotes Atherosclerosis in Mice via Dysregulated Innate Immunity [scRNA-seq]

2024-10-25 | GSE279601 | GEO

Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition

Project description:Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample.

2019-02-01 | PXD010701 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data