Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

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

ORGANISM(S): Danio rerio

PROVIDER: GSE176037 | GEO | 2021/12/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [I]

Project description:Clonal hematopoiesis (CH) results from enhanced fitness of a mutant hematopoietic stem and progenitor cell (HSPC), but how such clones expand is unclear. Here, we developed a technique that combines mosaic mutagenesis with color labeling of HSPCs to study how acquired mutations affect clonal fitness in a native environment. Mutations in CH-associated genes, like asxl1, promoted clonal dominance. Single-cell transcriptional analysis revealed that mutations stimulated expression of proinflammatory genes in mature myeloid cells and anti-inflammatory genes in progenitor cells of the mutant clone. Biallelic loss of one such immunomodulator, nr4a1, abrogated the ability of asxl1-mutant clones to establish clonal dominance. These results support a model where clonal fitness of mutant clones is driven by enhanced resistance to inflammatory signals from their mutant mature cell progeny.

2021-12-02 | GSE150373 | GEO

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [II]

2021-12-02 | GSE176036 | GEO

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

Project description:Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis

| PRJNA734615 | ENA

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [I]

Project description:Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [I]

| PRJNA631927 | ENA

Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [II]

Project description:Resistance to inflammation underlies enhanced fitness in clonal hematopoiesis [II]

| PRJNA734619 | ENA

Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-05-01 | E-GEOD-39418 | biostudies-arrayexpress

Clonal hematopoiesis is driven by aberrant activation of TCL1A

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-20 | GSE205637 | GEO

Obesity-induced inflammation exacerbates clonal hematopoiesis.

Project description:Characterized by the accumulation of somatic mutations in blood cell lineages, clonal hematopoiesis of indeterminate potential (CHIP) is frequent in aging and involves the expansion of mutated hematopoietic stem and progenitor cells (HSC/Ps) that leads to an increased risk of hematologic malignancy. However, the risk factors that contribute to CHIP-associated clonal hematopoiesis (CH) are poorly understood. Obesity induces a proinflammatory state and fatty bone marrow (FBM), which may influence CHIP-associated pathologies. We analyzed exome sequencing and clinical data for 47,466 individuals with validated CHIP in the UK Biobank. CHIP was present in 5.8% of the study population and was associated with a significant increase in the waist-to-hip ratio (WHR). Mouse models of obesity and CHIP driven by heterozygosity of Tet2, Dnmt3a, Asxl1, and Jak2 resulted in exacerbated expansion of mutant HSC/Ps due in part to excessive inflammation. Our results show that obesity is highly associated with CHIP and that a proinflammatory state could potentiate the progression of CHIP to more significant hematologic neoplasia. The calcium channel blockers nifedipine and SKF-96365, either alone or in combination with metformin, MCC950, or anakinra (IL-1 receptor antagonist), suppressed the growth of mutant CHIP cells and partially restored normal hematopoiesis. Targeting CHIP-mutant cells with these drugs could be a potential therapeutic approach to treat CH and its associated abnormalities in individuals with obesity.

| S-EPMC10231999 | biostudies-literature

Cancer therapy shapes the fitness landscape of clonal hematopoiesis.

Project description:Acquired mutations are pervasive across normal tissues. However, understanding of the processes that drive transformation of certain clones to cancer is limited. Here we study this phenomenon in the context of clonal hematopoiesis (CH) and the development of therapy-related myeloid neoplasms (tMNs). We find that mutations are selected differentially based on exposures. Mutations in ASXL1 are enriched in current or former smokers, whereas cancer therapy with radiation, platinum and topoisomerase II inhibitors preferentially selects for mutations in DNA damage response genes (TP53, PPM1D, CHEK2). Sequential sampling provides definitive evidence that DNA damage response clones outcompete other clones when exposed to certain therapies. Among cases in which CH was previously detected, the CH mutation was present at tMN diagnosis. We identify the molecular characteristics of CH that increase risk of tMN. The increasing implementation of clinical sequencing at diagnosis provides an opportunity to identify patients at risk of tMN for prevention strategies.

| S-EPMC7891089 | biostudies-literature

SRCAP Mutations Drive Clonal Hematopoiesis Through Epigenetic and DNA Repair Dysregulation

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-10-19 | GSE230155 | GEO