Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing analyisis to identify genes regulated by GW9662 in human cord blood hematopoietic stem and progenitor cells

ABSTRACT: PPARγ antagonist GW9662 treatment could enhance ex vivo expansion of human cord blood hematopoietic stem and progenitor cells (HSCs/HPCs). To gain mechanistical insights into how antagonizing PPARγ promotes expansion of HSCs/HPCs, we performed RNA sequencing (RNA seq) analysis to identify genes involved in this process. Loss of function of PPARγ in CB CD34+ cells resulted in downregulation of a number of differentiation associated genes, including CD38, CD1d, HIC1, FAM20C, DUSP4, DHRS3 and ALDH1A2, suggesting that PPARγ antagonist may maintain stemness of CB CD34+ cells, at least in part by preventing differentiation. We also observed that FBP1, encoding fructose 1, 6-bisphosphatase, a negative regulator of glycolytic flux, was significantly downregulated by treating CB CD34+ cells with GW9662. Our study demonstrates that antagonizing PPARγ signaling drives ex vivo expansion of human CB HSCs/HPCs by switching on FBP1 repressed glycolysis and preventing differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95703 | GEO | 2018/01/15

SECONDARY ACCESSION(S): PRJNA378166

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Expression data from infant ALL with MLL-AF4 rearrangement

2016-03-22 | GSE79450 | GEO

Expression data from infant ALL with MLL-AF4 rearrangement

Project description:MLL-AF4+ blasts from infant B-ALL, CB-derived CD34+CD38-CD19-CD33- HSC, CB-derived CD34+CD19+CD33- B-cell HPCs and CB-derived CD34+CD33+CD19- myeloid HPCs. We used microarray to estudy gene expression profile comparing ALL vs HSC, HPC and myeloid HPSC. We used highly FACS-purified (purity>98%) MLL-AF4+ blasts from infant B-ALL, CB-derived CD34+CD38-CD19-CD33- HSC, CB-derived CD34+CD19+CD33- B-cell HPCs and CB-derived CD34+CD33+CD19- myeloid HPCs. For each independent sample technical duplicates were always performed. Total RNA was extracted using TRIol reagent, and quantified on a Nanodrop spectrophotometer and Bioanalyzer. High-quality RNA was reverse transcribed and the obtained cDNA was used as a template to synthesize biotinylanted cDNA, then was fragmented and hybridized as duplicates/triplicates to HG-U133 plus2.0 GeneChips (Affymetrix) according to manufacturer's guideline.

2016-03-22 | E-GEOD-79450 | biostudies-arrayexpress

PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells

Project description:Cord blood hematopoietic stem cells (CB-HSCs) are an outstanding source for transplantation approaches. However, the amount of cells per donor is limited and culture expansion of CB-HSCs is accompanied by a loss of engraftment potential. In order to analyze the molecular mechanisms leading to this impaired potential we profiled global and local epigenotypes during the expansion of human CB hematopoietic stem and progenitor cells (HPSCs). Human CB-derived CD34+ cells were cultured in serum-free medium together with SCF, TPO, FGF, with or without Igfbp2 and Angptl5 (STF/STFIA cocktails). As compared to the STF cocktail, the STFIA cocktail maintains in vivo repopulation capacity of cultured CD34+ cells. Upon expansion, CD34+ cells genome-wide remodel their epigenotype and depending on the cytokine cocktail, cells show different H3K4me3 and H3K27me3 levels. Expanding cells without Igfbp2 and Angptl5 leads to higher global H3K27me3 levels. ChIPseq analyses reveal a cytokine cocktail-dependent redistribution of H3K27me3 profiles. Inhibition of the PRC2 component EZH2 counteracts the culture-associated loss of NOD scid gamma (NSG) engraftment potential. Collectively, our data reveal chromatin dynamics that underlie the culture-associated loss of engraftment potential. We identify PRC2 component EZH2 as being involved in the loss of engraftment potential during the in vitro expansion of HPSCs. 6 samples were hybridized GeneChip Human Gene 1.0 ST Arrays (Affymetrix)

2015-08-07 | E-GEOD-58461 | biostudies-arrayexpress

PRC2 inhibition counteracts the culture-associated loss of engraftment potential of human cord blood-derived hematopoietic stem and progenitor cells

2015-08-07 | GSE58461 | GEO

Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells

Project description:Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy. LGC006, a less potent SR1 analog, was also examined. KEYWORDS: two compounds, multiple doses, one time point two compounds, multiple doses, one time point

2011-04-04 | E-GEOD-28359 | biostudies-arrayexpress

Comparative analysis of gene expression by human Umblical Cord (UCB)-CD34+ Hematopoietic Stem Cells (HSCs) and human induced pluripotent stem (iPS) cell-derived CD34+ Hematopoietic Progenitor Cells (HPCs)

Project description:Hematopoietic stem and progenitor cells are a rare, self-renewing bone marrow resident population capable of giving rise to all circulating hematopoietic cells. They can be used therapuetically for reconstituting defective or ablated hematopoietic systems following chemotherapy, and for inducing tolerance toward allografts of the same haplotype as the HSC donor. There are several sources for HSCs, such as the adult bone marrow, or umblical cord blood, which is more replete with such HSCs. However, HSCs obtained from such sources may be immunogenic, especially if isolated from adult bone marrow. To overcome this issue, our lab has establsihed human induced pluripotent stem cell-derived HPCs with the hope of creating a nonimmunogenic, readily available and unlimited source of HSCs to use for therapy. The goal of this study was to compare the gene expression profiles of naturally found HSCs (UCB-CD34+ HSCs) and HPCs differentiated from 4 different human iPS cell lines (iPS-HPCs), so as to determine the variation between the four iPS-HPCs and whether there were any differences between these HPCs and naturally found HSCs. We utilized 4 iPS cells for this study (detailed descriptions are provided below). iPS cells were differentiated into hematopoietic progenitor cells by coculture on OP9 stromal cells, followed by enrichment of CD34+ cells through immunomagnetic bead separation. The UCB-CD34+ cells were isolated from frozen cord samples through immunomagnetic bead separation. Total RNA was isolated and human gene Affymetrix ST 1.0 arrays performed at the University of Iowa DNA core facility. Data was analyzed, normalized and plotted on BRB Array Tools.

2013-10-23 | E-GEOD-46888 | biostudies-arrayexpress

Adverse Effects of Bisphenol A and its substitute compounds on human SGBS preadipocytes

Project description:Bisphenol A (BPA), which is used in a variety of consumer-related plastic products, was reported to cause metabolic disruption. Substitute compounds are increasingly emerging, but are not sufficiently investigated. In this study, we aimed to investigate the mode of action of BPA and four of its substitutes during the differentiation of human preadipocytes. Human preadipocytes were exposed to BPA, BPS, BPB, BPF, and BPAF, as well as the PPARγ-antagonist GW9662. After 12 days of differentiation, global protein profiles were assessed using LC-MS/MS-based proteomics.

2021-08-05 | PXD023227 | Pride

Gene expression changes during hematopoietic cell differentiation

Project description:Gene expression analyses of hematopoietic stem cells (HSCs), progenitor cells (HPCs), and differentiated cell. Gene expressions of long-term HSCs (CD34-ckit+Sca1+Lineage-), short term HSCs (CD34+ckit+Sca1+Lineage-), Progenitor cells (ckit+Sca1- Lineage-), and differentiated cels (Lineage+) were examined by microarray. Results provide insight into the mechanism of hematopoietic cell differentiation. Long-term HSCs (CD34-ckit+Sca1+Lineage-), Short term-HSCs (CD34+ckit+Sca1+Lineage-), Progenitor cells (ckit+Sca1- Lineage-, and Lineage+), and differentiated cell (Lineage+) were sorted from mouse bone marraw and were examined by microarray. Results provide insight into the mechanism of hematopoietic cell differentiation.

2013-11-06 | E-GEOD-48986 | biostudies-arrayexpress

Gene expression changes during hematopoietic cell differentiation

2013-11-06 | GSE48986 | GEO

MYCT1 Controls Environmental Sensing in human Hematopoietic Stem Cells [scRNA-seq Dextran]

Project description:We identified a novel HSC regulatory gene, MYCT1 (MYC target 1), that is selectively expressed in undifferentiated human HSPC and is critical for human HSC expansion and engraftment. MYCT1 knockdown (KD) in human fetal liver and cord blood (CB) HSPCs impaired expansion ex vivo and engraftment after transplantation, whereas restoring the compromised MYCT1 expression via lentiviral overexpression (OE) in cultured human CB HSPCs improved ex vivo expansion of the most undifferentiated human HSPCs (CD34+CD38-CD90+CD45RA-EPCR+ITGA3+) and enhanced their engraftment ability. We performed single cell RNAseq of uncultured human CB HSPCs, as well as 72 hours after MYCT1 KD and OE to identify MYCT1-regulated programs in HSC and understand the role of MYCT1 in governing human HSPC expansion and engraftment ability. Functional enrichment analysis linked the loss of MYCT1 in HLF+ HSCs to a profound dysregulation of multiple cellular programs essential for HSC stemness, such as oxidative phosphorylation or proteostasis, while MYCT1 OE had the opposite effect and showed closer similarity to uncultured HLF+ HSCs. These data indicate that the loss or gain of MYCT1 expression elicits major effects on programs regulating human HSC functional competence. Mechanistically, we found that MYCT1 governs endocytosis. Therefore, we performed scRNAseq of cultured HSPCs (CD34+CD38-CD90+EPCR+) with low, medium or high levels of endocytosis and found that low endocytosis HSCs had higher MYCT1 expression and favorable transcriptomic profiles of HSC functional competence.

2024-04-08 | GSE254857 | GEO

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