Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GSK-3Î² inhibition promotes engraftment of ex vivo expanded hematopoietic stem cells

ABSTRACT: Glycogen synthase kinase-3Î² (GSK-3Î²) has been recently identified as an important regulator of stem cell function. In vitro studies show that GSK-3Î² inhibition delays proliferation of human haematopoietic progenitor cells while increasing numbers of late dividing multipotent progenitors. Gene expression analysis revealed that GSK-3Î² inhibition modulates the expression of a subset of genes that are transcriptional targets for cytokines. GSK-3Î² inhibition antagonised down-regulation of genes encoding cyclin dependent kinase inhibitor p57 and a member of the growth arrest and DNA damage 45 family, GADD45B as well as up-regulation of cyclin D1 by cytokines, providing a possible mechanism for the BIO-induced delay in cell cycle progression. Surprisingly, inhibition of GSK-3Î² earlier shown to prevent Î²-catenin degradation and promote the nuclear accumulation of Î²-catenin was not sufficient to activate its transcriptional targets in haematopoietic stem cells. GSK-3Î² inhibition up-regulated the expression of a several positive regulators of stem cell function suppressed during cytokine-induced proliferation. The data supports a clinical role for GSK-3Î² inhibition to improve engraftment efficiency of ex vivo expanded stem cells. Total RNA was isolated from three groups following expansion of CD34+ cells in cytokikes and then treatment with BIO, as described below.

ORGANISM(S): Homo sapiens

SUBMITTER: Kap-hyoun Ko

PROVIDER: E-GEOD-21073 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

GSK-3β inhibition promotes engraftment of ex vivo expanded hematopoietic stem cells

Project description:Glycogen synthase kinase-3β (GSK-3β) has been recently identified as an important regulator of stem cell function. In vitro studies show that GSK-3β inhibition delays proliferation of human haematopoietic progenitor cells while increasing numbers of late dividing multipotent progenitors. Gene expression analysis revealed that GSK-3β inhibition modulates the expression of a subset of genes that are transcriptional targets for cytokines. GSK-3β inhibition antagonised down-regulation of genes encoding cyclin dependent kinase inhibitor p57 and a member of the growth arrest and DNA damage 45 family, GADD45B as well as up-regulation of cyclin D1 by cytokines, providing a possible mechanism for the BIO-induced delay in cell cycle progression. Surprisingly, inhibition of GSK-3β earlier shown to prevent β-catenin degradation and promote the nuclear accumulation of β-catenin was not sufficient to activate its transcriptional targets in haematopoietic stem cells. GSK-3β inhibition up-regulated the expression of a several positive regulators of stem cell function suppressed during cytokine-induced proliferation. The data supports a clinical role for GSK-3β inhibition to improve engraftment efficiency of ex vivo expanded stem cells.

2010-03-26 | GSE21073 | GEO

Functional and genetic heterogeneity of distinctive leukaemic stem cell populations in CD34- human Acute Myeloid Leukaemia

Project description:We performed RNA-sequencing of normal haematopoietic stem cells and progenitor populations and of Leukemic Stem Cells in CD34- Acute Myeloid Leukaemia.

2016-06-22 | E-MTAB-2672 | biostudies-arrayexpress

Transcriptional profiling of CML and normal, stem and progenitor haematopoietic cells.

Project description:Transcriptional profiling of four cell populations to understanding chronic myeloid leukaemia in humans. The populations are normal haematopoietic stem cells (HSC), normal progenitor cells (HPC), CML stem cells (LSC) and CML progenitor cells (LPC).

2016-05-26 | E-MTAB-2581 | biostudies-arrayexpress

Extracts from sweet sorghum (Sorghum bicolor), a feedstock for biorefining, suppressed proliferation and elevated apoptosis in human colon cancer stem cells via suppression of Wnt/beta-catenin signaling pathway

Project description:In colorectal cancer, p53 is commonly inactivated, associated with chemo-resistance, and marks the transition from non-invasive to invasive disease. Cancers, including colorectal cancer, are thought to be diseases of aberrant stem cell populations, as stem cells are able to self-renew, making them long-lived enough to acquire mutations necessary to manifest the disease. We have shown that extracts from sweet sorghum stalk components eliminate colon cancer stem cells (CCSC) in a partial p53-dependent fashion. However, the underlying mechanisms are unknown. In the present study, CCSC were transfected with short hairpin-RNA against p53 (CCSC p53 shRNA) and treated with sweet sorghum phenolics extracted from different plant components (dermal layer, leaf, seed head and whole plant). While all components demonstrated anti-proliferative and pro-apoptotic effects in CCSC, phenolics extracted from the dermal layer and seed head were more potent in eliminating CCSC by elevating caspases 3/7 activity, PARP cleavage, and DNA fragmentation in a p53-dependent and p53-independent fashion, respectively. Further investigations revealed that the anti-proliferative and pro-apoptotic effects were associated with decreases in beta-catenin protein levels, and beta-catenin targets cyclin D1, cMyc, and survivin. These results suggest that the anti-proliferative and pro-apoptotic effects of sweet sorghum extracts against human colon cancer stem cells are via suppression of Wnt/beta-catenin pro-survival signaling in a p53-dependent (dermal layer) and partial p53-independent (seed head) fashion. LCMS used to identify phenolic compounds associated with extract activity

2014-05-01 | MTBLS69 | MetaboLights

Î²-cateinin activation in hair follicle dermal sheath induces ectopic hair outgrowth and skin fibrosis

Project description:Dermal sheath (DS) shows potent hair inducing capability and high plasticity without leading to immuno rejection. A recent study showed a subset of DS cells, identified as hair follicle (HF) dermal stem cells, can be mobilized to regenerate DS, maintain/supply the cell number of dermal papilla (DP) and modulate hair type. However, it is unclear how Wnt/Î²-catenin signaling regulates DS cells behaviors. Here we report that activation of Î²-catenin in DS, to some extent, endows it with hair inducing ability, reprogramming HF epidermal cells to generate new outgrowth. The new formed dermal condensates (DC)/DP lying adjacent the outgrowth derives from DS and/or its progeny, and homeostasis of pre-existing HFs is disturbed. Additionally, progressive skin fibrosis is prominent in hypodermis, where the excessive activated fibroblasts at least partially originate from DS and/or its progeny. Gene expression analysis of purified DS cells revealed that 44% DC signature genes are regulated, most of which are up-regulated. We found elevated expression of several growth factors, including Noggin, Fgf7 and Fgf10, which were previously implicated in HF induction. In summary, we confirm the high plasticity of DS cells by in vivo assays and report a mechanism by which Wnt/Î²-catenin signaling controls DS cells behaviors. We prospectively isolated control and cÎex3 DS cells (YFP+ve CD34-ve ALP-ve ITGÎ±8-ve cells) from P15 dorsal skins by FACS.

2016-05-31 | E-GEOD-81615 | biostudies-arrayexpress

Gene expression analysis in mouse embryonic stem cells containing Î²-catenin lysine 49 to alanine mutation

Project description:Î²-Catenin is the major co-regulator of the Wnt signalling pathway. Î²-Catenin lysine 49 is post-translationally modified. The histone methyl transferase Ezh2 trimethylates Î²-catenin at lysine 49 and the acetyl transferase Cbp acetylates Î²-catenin at the same lysine. To determine the effects on gene expression embryonic stem cells containing either a Gfp tagged Î²-catenin wildtype (wt) or lysine 49 to alanine (K49A) loss of function mutation were analysed by micro array expression profiling. To determine the effects on gene expression in the pluripotent state two biological replicates of Gfp Î²-catenin wt and Gfp Î²-catenin K49A were analysed. The results showed that genes which affect pluripotency as well as differentiation were altered by Î²-catenin K49A mutation. To analyse the effects of gene expression during ES cell differentiation ES cells containing Gfp Î²-catenin wt or K49A were differentiated into mesodermal progenitors (mp) and neuronal progenitors (np). Two biological replicates were analysed by micro array expression profiling. Differentially expressed genes between Gfp Î²-catenin wt and K49A during differentiation were observed. Mesodermal marker genes like t-brachyury and cdx2 were not upregulated in mesodermal differentiation of Gfp Î²-catenin K49A Es cells.

2017-03-21 | E-MTAB-5523 | biostudies-arrayexpress

Human iPSC-based model for Duchenne muscular dystrophy

Project description:We developed a novel somite-based step-wise strategy for the efficient derivation of functional human myocytes, suggesting that past failures were due to incomplete specification. Treatment with two small molecules inhibiting glycogen synthase kinase 3Î² (GSK-3Î²) and the Notch signaling pathway in undifferentiated hPSCs results in the formation of somite-like cells by Day 4 and, subsequently contractile myotubes in vitro around Day 25 with the ability to engraft and actively participate in muscle repair in vivo. Antibody-based purification can enrich homogenous myocyte populations exhibiting genuine myogenic molecular and cellular characteristics, including extraocular muscle-like features. Furthermore, hPSCs derived from patients with multiple neuromuscular diseases successfully give rise to patient-specific skeletal muscle cells bearing signature phenotypes. Human embryonic stem cell were differentiated to skeletal muscle and compared to non-differentiated cells in triplicate biological replicates. For the confirmation of differentiated cell's characteristics and the global mRNA profiles, We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Further more, we used microarrys for the comparing control and disease gene expression profiles, again in triplicate.

2016-06-16 | E-GEOD-70955 | biostudies-arrayexpress

Differential gene expression of Wnt agonist (BIO and lithium chloride) treated human dental pulp stem cells

Project description:Small molecules, BIO and Lithium chloride are widely used to activate Wnt signaling. It has been shown that these molecules induced beta-catenin accumulation and translocation, leading to the activation of Wnt signaling. These molecules also control various cell responses. Here, the differential gene expression of human dental pulp stem cells treated with BIO and Lithium chloride was examined using a high throughput RNA sequencing technique. Results demonstrated that BIO and Lithium chloride regulated the mRNA expression of various genes in human dental pulp stem cells.

2022-08-17 | GSE183633 | GEO

Wnt/β-catenin signaling activation induces differentiation in human limbal epithelial stem cells cultured ex vivo

Project description:hLESC ex vivo cultures treated with GSK-3 inhibitor LY2090314 (small molecule) to activate Wnt/β-catenin signaling and further examine the impact of canonical Wnt/β-catenin signaling activation on hLESCs. We used microarray to explore the changes in gene expression in GSK-3 inhibitor LY2090314 treated and untreated ex vivo cultures of hLESCs to examine gene expression changes upon Wnt/β-catenin signaling activation in hLESCs.

2023-06-26 | GSE234403 | GEO

Transcription profiling of human CD34 cDNA over-expressing human CD34+ cells

Project description:In order to investigate the role of CD34 antigen in haematopoietic commitment, we overexpressed the human CD34 cDNA in human CD34+ cells by retroviral gene transfer. Experiment Overall Design: In a set of 10 independent experiments, gene transfer efficiency, assessed by flow cytometry analysis of ÎLNGFR positivity, ranged 15 to 30%. Transduced cells were than purified for NGFR expression at day 3 of liquid culture with the retroviral vector. Phenotypic analysis, performed on transduced/NGFR purified cells evidenced that the CD34 transgene was highly expressed at the protein level (80% of LCD34IÎN vs 30% of controls at 5 days post-infection) up to 14 days of liquid culture.

2008-06-18 | E-GEOD-8003 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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