GEO DataSets

(Submitter supplied) 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. more...

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20828

8 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL20828 GPL24995

16 Samples

Download data

(Submitter supplied) 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. more...

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24995

8 Samples

Download data: RDS

(Submitter supplied) Splenic CD11b+ and CD4+ cells were isolated from Dnmt3a+/+ or Dnmt3aR878/+ mice using LS columns on the magnetic field of QuadroMACS Separator according to the manufacturer’s instructions (Miltenyi Biotec), and the High-Molecular-Weight (HMW) DNA of cells were isolated using MagAttract HMW DNA Kit according to the manufacturer’s instructions (Qiagen). WGBS was performed using the Zymo-Seq WGBS Library Kit (Zymo research) according to the manufacturer’s recommendations at the High Throughput Sequencing Core of Children’s Hospital of Philadelphia, PA, USA. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL24247

18 Samples

Download data: TXT

(Submitter supplied) Dnmt3a-mutant mouse HSCs, but not control HSCs are able to maintain clonality during type II inteferson signaling. To investigate the molecular mechanism of this observation, we investigated IFNg-incuded changes in DNA methylome of mouse HSCs in a mouse model. In the model, we transplanted 10% CD45.2 donor BM cells, 10% CD45.1/2-GFP competitors and 80% CD45.1 BM cells into CD45.1 recipients. In the treatment group, we transplated the CD45.1 BM cells with the genotype of IFNgrKO; rtTA-M2; Tet-O-IFNg to induce a chronic IFNg exposure. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL21493 GPL24247

56 Samples

Download data: BED, MTX, TSV

(Submitter supplied) Clonal hematopoiesis resulting from enhanced fitness of mutant hematopoietic stem cells (HSCs) associates with both favorable and unfavorable health outcomes related to the types of mature mutant blood cells produced, but how this lineage output is regulated is unclear. Using a mouse model of DNMT3AR882/+ clonal hematopoiesis (Dnmt3aR878H/+), we found that aging-induced TNFα signaling promoted the selective advantage of mutant HSCs as well as stimulated mutant B lymphoid cell production. more...

Organism:

Mus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL31136

14 Samples

Download data: TSV

(Submitter supplied) Clonal hematopoiesis of aging results from enhanced fitness of mutant hematopoietic stem cells (HSCs) and associates with both favorable and unfavorable health outcomes related to lineage cell types produced by mutant HSCs. The extent to which lineage output can be controlled in clonal hematopoiesis is unknown. Using a mouse model of DNMT3AR882/+ clonal hematopoiesis (Dnmt3aR878H/+), we find that aging-induced TNFα signaling drives selective advantage of mutant HSCs concomitant with B lymphoid lineage production. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL19057

28 Samples

Download data: TXT

(Submitter supplied) Mutations in additional sex combs like 1 (ASXL1) confer poor prognosis in myeloid malignancies and are also found in pre-malignant clonal hematopoiesis of indeterminate potential (CHIP). However, the mechanisms by which these mutations contribute to disease initiation remain unresolved and therapeutic targeting has remained elusive. Here, we demonstrate that ASXL1 mutations are frequently founding lesions in acute myeloid leukemia (AML) and lead to the expression of a functional, truncated protein. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL24676

35 Samples

Download data: BW, TSV

(Submitter supplied) The prevalence of clonal haematopoiesis of indeterminate potential (CHIP) in healthy individuals increases rapidly from age 60 onwards and has been associated with increased risk for malignancy, heart disease and ischemic stroke. CHIP is driven by somatic mutations in stem cells that are also drivers of myeloid malignancies. Since mutations in stem cells often drive leukaemia, we hypothesised that stem cell fitness substantially contributes to transformation from CHIP to leukaemia. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL21697

261 Samples

Download data: TSV

(Submitter supplied) Hematopoietic stem and progenitor cells (HSPCs) are able to self-renew and can give rise to all blood lineages throughout their lifetime, yet the mechanisms regulating HSPC development have yet to be discovered. In this study, we characterized a hematopoiesis defective zebrafish mutant line named smu07, which was obtained from our previous forward genetic screening, and found the HSPC expansion deficiency in the mutant. more...

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24995

4 Samples

Download data: CSV

(Submitter supplied) Epigenetic modifying enzymes DNMT3A and TET2 are recurrently mutated in hematological disorders despite possessing opposing biochemical functions in the DNA methylation processes. Using conditional ablation, we show these contrasting genotypes result in different functional effects in hematopoietic stem cells (HSCs). Loss of Dnmt3a bestows enhanced self-renewal on HSCs in serial, competitive repopulation assays while Tet2 loss functionally depletes HSCs after a tertiary transplant despite an initial competitive advantage. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL19057 GPL24247

36 Samples

Download data: BW, TSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Danio rerio

Type:

Expression profiling by array

Platforms:

GPL18413 GPL23085 GPL21741

97 Samples

Download data: TXT

(Submitter supplied) To characterize the distinct features of HSPCs and relevant niche cells, we performed RNA-seq with sorted zebrafish HSPCs and niche cells, based on fluorescent protein labeling from distinct regions at six relatively discrete stages.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21741

24 Samples

Download data: TXT

(Submitter supplied) To decode the complexed mechanism controlling HSC expansion, from the viewpoint of systems biology, we performed spatial transcriptome analysis by dissecting the whole hematopoietic organ, CHT.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18413

72 Samples

Download data: TXT

(Submitter supplied) To investigate the peculiarity of CHT HSPCs, as well as the interaction of CHT niche and HSPCs at higher resolution, we performed scRNA-seq with zebrafish CHT.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23085

1 Sample

Download data: TXT

(Submitter supplied) To profile the developmental landscape of fetal HSPCs and their local niche, here, by using single-cell RNA-sequencing, we decoded the expanding hematopoietic organ in zebrafish

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing; Third-party reanalysis

Platform:

GPL23085

2 Samples

Download data: TXT

(Submitter supplied) Multiple signaling pathways contribute to blood cell formation in the fetus, but a role for innate immune/inflammatory signaling has not been described. Here we show that mouse fetuses deficient for either interferon gamma 1 (IFNg) or its receptor have decreased numbers of lymphoid progenitors and hematopoietic stem cells (HSCs) in the aorta/gonad/mesonephros region and placenta. The role of IFNg signaling was evolutionarily conserved, as morpholino knockdown of IFNg and its receptor reduced the number of hematopoietic stem and progenitor cells in the dorsal aorta and caudal hematopoietic territory of zebrafish embryos, and rag2 expressing cells in the thymus. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL10333

8 Samples

Download data: TXT

(Submitter supplied) ANGPTL2 is a protein in the angiopoietin-like protein family and plays a role in hematopoietic and vascular physiology. This study examined the effects of ANGPTL2 on CD34+ human hematopoetic progenitor cells.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL9115

2 Samples

Download data: WIG

(Submitter supplied) ANGPTL2 is a protein in the angiopoietin-like protein family and plays a role in hematopoietic and vascular physiology. This study examined the effects of ANGPTL2 on CD34+ human hematopoetic progenitor cells.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

6 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Danio rerio

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20828

7 Samples

Download data: TSV