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SRP093978
Homo sapiens
30 Downloadable Samples
Illumina HiSeq 2500
Description
The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties. Overall design: Gene expression analysis of in vitro expanded human HSPCs (CD34+ cells) by valproic acid
Publication Title
Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells.
Sample Metadata Fields
Disease, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.
Publication Title
LXR is a negative regulator of glucose uptake in human adipocytes.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Polycystic Kidney Disease is characterized by the formation of large fluid-filled cysts that eventually destroy the renal parenchyma leading to end-stage renal failure. Although remarkable progress has been made in understanding the pathologic mechanism of the disease, the precise orchestration of the early events leading to cyst formation is still unclear. Abnormal cellular proliferation was traditionally considered to be one of the primary irregularities leading to cyst initiation and growth. Consequently, many therapeutic interventions have focused on targeting this abnormal proliferation, and some have even progressed to clinical trials. However, the role of proliferation in cyst development was primarily examined at stages where cysts are already visible in the kidneys and therefore at later stages of disease development. In this study we focused on the cystic phenotype since birth in an attempt to clarify the temporal contribution of cellular proliferation in cyst development. Using a PKD2 transgenic rat model (PKD2 (1-703)) of different ages (0-60 days after birth) we performed gene expression profiling and phenotype analysis by measuring various kidney parameters. Phenotype analysis demonstrated that renal cysts appear immediately after birth in the PKD2 transgenic rat model (PKD2 (1-703)). On the other hand, abnormal proliferation occurs at later stages of the disease as identified by gene expression profiling. Interestingly, other pathways appear to be deregulated at early stages of the disease in this PKD model. Our data suggest that cystogenesis precedes deregulation of proliferation-related pathways, suggesting that proliferation abnormalities may contribute in cyst growth rather than cyst formation.
Publication Title
Cyst formation in the PKD2 (1-703) transgenic rat precedes deregulation of proliferation-related pathways.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Regulation of genes in shoots and roots and Arabidopsis in response to Zn-deficiency in wild-type and hma2 hma4 mutants plants
Publication Title
Systemic Upregulation of MTP2- and HMA2-Mediated Zn Partitioning to the Shoot Supplements Local Zn Deficiency Responses.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana, Arabidopsis lyrata, Arabidopsis halleri
- 2 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Gene copy number variation (CNV) is a form of genetic polymorphism that contributes significantly to genome size and function but remains poorly characterized due to technological limitations. Inter-specific comparisons of CNVs in recently diverged plant species are crucial to uncover selection patterns underlying adaptation of a species to stressful environments. Especially given that gene amplifications have long been implicated in emergence of species-specific traits, we conducted a genome-wide survey to identify species-specific gene copy number expansions and deletions in the model extremophile species - Arabidopsis halleri that has diverged in evolutionarily recent time from Arabidopsis thaliana.
Publication Title
Between-species differences in gene copy number are enriched among functions critical for adaptive evolution in Arabidopsis halleri.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smoking is a major risk factor for Urothelial carcinoma (UC). However the complex mechanisms, how smoking promotes carcinogenesis and tumour progression, remain obscure. A microarray based approached was therefore performed to detect the smoking derived gene expression alteration in non-malignant and malignant urothelial tissues from patients with superficial or invasive UC. Smoking enhanced cell migration and response to tissue damages. In non-malignant tissues smoking induced immune response and altered the cytoskeleton. In urothelial carcinoma, smoking altered extracellular and chromosome structures. Smoking affected tissues from patients with invasive carcinomamore strongly, up-regulating particularly growth factors and oncogenes in non-malignant tissue of patients with invasive but not with superficial carcinoma. In former smokers, comparable changes were seen in tissues form patients with invasive disease while they were minor or reversed in tissue of patients with superficial disease. Best but not complete tissue repair was suggestedfor non-malignant tissue from patients with superficial tumours.
Publication Title
New insights into the influence of cigarette smoking on urothelial carcinogenesis: smoking-induced gene expression in tumor-free urothelium might discriminate muscle-invasive from nonmuscle-invasive urothelial bladder cancer.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
MS-275 and hydroxyurea treatment influences whole gene expression including DNA damage response and cell cycle checkpoint signaling.
Publication Title
HDAC1 and HDAC2 integrate checkpoint kinase phosphorylation and cell fate through the phosphatase-2A subunit PR130.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression analysis performed on FACS sort purified GC LZ and DZ cells of either high or low affinity to identify unique gene signatures.
Publication Title
Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression analysis performed on FACS sort purified GC LZ and DZ cells of either high and low affinity to identify unique gene signatures.
Publication Title
Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
N-octanoyl dopamine (NOD), but not dopamine dose dependently induces the UPR. This was also found for other synthetic N-Acyl dopamine derivates (NADD). Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury.
Publication Title
N-octanoyl dopamine treatment of endothelial cells induces the unfolded protein response and results in hypometabolism and tolerance to hypothermia.
Sample Metadata Fields
Cell line, Treatment
View Samples