Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression data from human bone marrow hematopoietic stem cells

ABSTRACT: In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process.

ORGANISM(S): Homo sapiens

PROVIDER: GSE32719 | GEO | 2011/11/11

SECONDARY ACCESSION(S): PRJNA146789

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling by array of human bone marrow hematopoietic stem cells from healthy young and elderly individuals

Project description:In the human hematopoietic system, aging is associated with decreased bone marrow cellularity, decreased adaptive immune system function, and increased incidence of anemia and other hematological disorders and malignancies. Recent studies in mice suggest that changes within the hematopoietic stem cell (HSC) population during aging contribute significantly to the manifestation of these age-associated hematopoietic pathologies. While the mouse HSC population has been shown to change both quantitatively and functionally with age, changes in the human HSC and progenitor cell populations during aging have not yet been characterized. Gene expression profiling revealed that aged human HSC transcriptionally up-regulate genes associated with cell cycle, myeloid lineage specification, and myeloid malignancies. These age-associated alterations in the frequency, function, and gene expression profile of human HSC are significantly similar to those changes observed in mouse HSC, suggesting that hematopoietic aging is an evolutionarily conserved process. In order to elucidate the properties of an aged human hematopoietic system that may predispose to age-associated hematopoietic dysfunction, we evaluated HSC and other hematopoietic progenitor populations from healthy, hematologically normal young and elderly human bone marrow samples. We found that aged human HSC increase in frequency, are less quiescent, and exhibit myeloid-biased differentiation potential compared to young HSC.

2011-11-11 | E-GEOD-32719 | biostudies-arrayexpress

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia

Project description:Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML.

2019-05-11 | GSE104379 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-seq of KLF6 KO)

2019-05-13 | GSE121560 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-Seq of LMNA KD)

2019-05-13 | GSE116254 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (H3 ChIPseq)

2019-05-13 | GSE106422 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (RNA-Seq of HSCe)

2019-05-13 | GSE104406 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (ERRBS)

2019-05-13 | GSE104405 | GEO

Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia (ChIP-seq)

2019-05-13 | GSE104404 | GEO

Altered microRNA expression links IL6 and TNF-induced inflammaging with myeloid malignancy [miR146aKO_LSK_WGBS]

Project description:Aging is associated with significant changes in the hematopoietic system, including increased inflammation, impaired hematopoietic stem cell (HSC) function, and increased incidence of myeloid malignancy. Inflammation of aging (“inflammaging”) has been proposed as a driver of age-related changes in HSC function and myeloid malignancy, but mechanisms linking these phenomena remain poorly defined. Here, we identify loss of miR-146a as driving aging-associated inflammation in AML patients. miR-146a expression declined in old wild-type mice, and loss of miR-146a promoted premature HSC aging and inflammation in young miR-146a-null mice, preceding development of aging-associated myeloid malignancy. Using single-cell assays of HSC quiescence, stemness, differentiation potential, and epigenetic state to probe HSC function and population structure, we found that loss of miR-146a depleted a subpopulation of primitive, quiescent HSCs. DNA methylation and transcriptome profiling implicated NF-κB, IL6, and TNF as potential drivers of HSC dysfunction, activating an inflammatory signaling relay promoting IL6 and TNF secretion from mature miR-146a-/- myeloid and lymphoid cells. Reducing inflammation by targeting Il6 or Tnf was sufficient to restore single-cell measures of miR-146a-/- HSC function and subpopulation structure, and reduced the incidence of hematological malignancy in miR 146a-/- mice. miR-146a-/- HSCs exhibited enhanced sensitivity to IL6 stimulation, indicating that loss of miR-146a affects HSC function via both cell-extrinsic inflammatory signals and increased cell-intrinsic sensitivity to inflammation. Thus, loss of miR 146a regulates cell-extrinsic and -intrinsic mechanisms linking HSC inflammaging to the development of myeloid malignancy.

2020-05-14 | GSE148989 | GEO

Altered microRNA expression links IL6 and TNF-induced inflammaging with myeloid malignancy [miR146aKO_ESLAM_SCBS]

2020-05-14 | GSE148988 | GEO