ImmunoAgeing Colonies WGS
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001004280 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Whole-genome sequencing of 288 single-cell-derived blood colonies from 3 elderly individuals with clonal haematopoiesis.
| EGAD00001007684 | EGA
Project description:This data presents the transcriptomes of bulk mature colonies derived from single human haematopoietic stem cells / multipotent progenitors (HSC/MPPs) and granulocyte macrophage progenitors (GMPs) purified from one indiviual with age related clonal haematopoisesis. The profiled colonies contain mature monocytes, as measured by conventional cell surface markers (CD14+, CD15-, GlyA-), but no other mature blood cell types. This dataset is part of a larger study, the main objective of which is to understand the functional effects conferred by somatic DNMT3A R882H mutation on human haematopoietic stem cell differentiation capacity. In clonal haematopoiesis, DNMT3A R882H and DNMT3A WT HSPCs co-exist in the same individual. We compared the transcriptional differences between mature monocytic colonies derived from DNMT3A R882H and WT HSPCs in vitro. Analysis of this dataset shows that, in this individual, DNMT3A R882H HSPCs produce less mature monocytes than their WT counterparts over the same culture time.
2023-08-28 | GSE241520 | GEO
Project description:Human multipotent stromal cells readily form single-cell-derived colonies when plated at clonal densities. However, the colonies are heterogeneous because cells from a colony form new colonies that vary in size and differentiation potential when replated at clonal densities. The experiments here tested the hypothesis that cells in the inner regions of colonies are partially differentiated, but the differentiation is reversible. Cells were separately isolated from the dense inner (IN) regions and less-dense outer regions (OUT) of single-cell-derived colonies. Cells were then compared by assays of their transcriptomes and proteins, and for clonogenicity and differentiation. IN cells expressed fewer cell-cycle genes and higher levels of genes for extracellular matrix than the OUT cells. When transferred to differentiation medium, differentiation of the colonies occurred primarily in the IN regions. However, the IN cells were indistinguishable from OUT cells when replated at clonal densities and assayed for rates of propagation and clonogenicity. Also, colonies formed by IN cells were similar to colonies formed by OUT cells because they had distinct IN and OUT regions. Cultures of IN and OUT cells remained indistinguishable through multiple passages (30-75 population doublings), and both cells formed colonies that were looser and less dense as they were expanded. The results demonstrated that cells in the IN region of single-cell-derived colonies are partially differentiated, but the differentiation can be reversed by replating the cells at clonal densities.
2008-10-07 | GSE13002 | GEO
Project description:Human multipotent stromal cells readily form single-cell-derived colonies when plated at clonal densities. However, the colonies are heterogeneous because cells from a colony form new colonies that vary in size and differentiation potential when replated at clonal densities. The experiments here tested the hypothesis that cells in the inner regions of colonies are partially differentiated, but the differentiation is reversible. Cells were separately isolated from the dense inner (IN) regions and less-dense outer regions (OUT) of single-cell-derived colonies. Cells were then compared by assays of their transcriptomes and proteins, and for clonogenicity and differentiation. IN cells expressed fewer cell-cycle genes and higher levels of genes for extracellular matrix than the OUT cells. When transferred to differentiation medium, differentiation of the colonies occurred primarily in the IN regions. However, the IN cells were indistinguishable from OUT cells when replated at clonal densities and assayed for rates of propagation and clonogenicity. Also, colonies formed by IN cells were similar to colonies formed by OUT cells because they had distinct IN and OUT regions. Cultures of IN and OUT cells remained indistinguishable through multiple passages (30-75 population doublings), and both cells formed colonies that were looser and less dense as they were expanded. The results demonstrated that cells in the IN region of single-cell-derived colonies are partially differentiated, but the differentiation can be reversed by replating the cells at clonal densities. Experiment Overall Design: In this study heterogeneity of human multipotent stromal cells in single-cell-derived colonies was examined. Cells were grown as colonies on slides for 12 days and cells from inside (IN) and outside (OUT) of colonies were isolated with laser capture microdissection. Cells from two colonies were pooled for each sample. This study consists of 3 biological replicates for each colony region (3 for IN and 3 for OUT). All 6 samples were run on Affymetrix microarrays after amplification and labeling using Nugen Ovation technology.
2008-10-26 | E-GEOD-13002 | biostudies-arrayexpress
Project description:An investigation of mutation timing in clonal haematopoiesis
| EGAS00001003933 | EGA
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.
2020-03-12 | GSE146812 | GEO
Project description:The study will measure blood population dynamics in abnormal human haematopoiesis in patients with clonal blood stem cell disorders.
| EGAS00001003181 | EGA
Project description:Gene expression profile of individual CFU-GM colonies identified as uniallelic TET2 mutant versus TET2 wild type was analyzed via RNA-Seq to verify the impact of TET2 editing on gene expression in the rhesus macaque clonal hematopoiesis model.
2022-06-22 | GSE148132 | GEO
Project description:Recent epidemiological studies have shown that cancer-associated DNMT3A mutations can be detected in the blood of a large proportion of asymptotic elderly individuals. It is important to understand how these mutations provide a competitive advantage to HSCs and allow them to establish clonal dominance. Here we demonstrate that the stress of serial HSC transplantation immortalizes Dnmt3a-null HSCs.
2018-04-25 | GSE98186 | GEO