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Danio rerio
100 Downloadable Samples
NextSeq 500
Description
Germ plasm, the Balbiani body and nuage are evolutionary conserved structures essential for germ cell specification and maintenance. We describe Tdrd6a as a component of these structures with two distinct molecular functions. First, Tdrd6a facilitates the accumulation of the typical antisense-bias of piRNAs, without having effects on piRNA biogenesis signatures. Second, we show that Tdrd6a is required for Balbiani body and germ plasm integrity, and associates with RNA-binding proteins and germ plasm mRNAs. On the cell-biological level, maternally contributed Tdrd6a strongly impacts germ cell formation, but is dispensable for fertility. Using single-cell RNA-sequencing we demonstrate that Tdrd6a promotes early germ cell development and regulates the stoichiometry of germ plasm mRNAs. We propose that Tdrd6a functions as a scaffold to recruit correct ratios of germ plasm transcripts and to accumulate antisense piRNA complexes in order to ensure both specification and maintenance of germ cells. Overall design: Single cell were sorted directly in Trizolfrom embryos spawned by mz tdrd6a-/- mother and wt mother carrying a kop::egfp-f-nos1-3'UTR transgene. Thereafter single cell trizol extractio was performed followed by RT, IVT and RNA-seq library prep.
Publication Title
Tdrd6a Regulates the Aggregation of Buc into Functional Subcellular Compartments that Drive Germ Cell Specification.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Extracellular nucleotides are potent signaling molecules mediating cell-specific biological functions. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation while stimulating the migration, in vitro and in vivo, of human bone marrow-derived mesenchymal stem cells (BM-hMSC). Here, we investigated the effects of ATP on BM-hMSC differentiation capacity.
Publication Title
Extracellular purines promote the differentiation of human bone marrow-derived mesenchymal stem cells to the osteogenic and adipogenic lineages.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the present study, we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization.
Publication Title
Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice.
Sample Metadata Fields
Specimen part
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GSE14566- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Nucleotides triphosphates are extracellular messengers binding to specific plasma membrane receptors (P2Rs) that modulate responses as different as proliferation, differentiation, migration or cell death on several cell types including hematopoietic stem cells. Little and controversial information is available on the role of extracellular nucleotides in human mesenchimal stem cells (hMSCs). In this study, we assessed whether P2Rs are expressed and functional in bone marrow-derived hMSCs. Our results demonstrated, at the mRNA and protein level, the expression of all P2X and P2Y receptor subtypes identified so far. P2R activation by their natural ligands adenosine triphosphate (ATP) and uridine triphosphate (UTP) induced in hMSCs, intracellular Ca2+ concentration changes, plasma membrane depolarization and permeabilization. hMSCs were resistant to the cytotoxic effects of high dose ATP despite the expression of permeabilizing P2Rs as demonstrated by the lack of morphological changes, significant release of intracellular markers of cell death or modification of the mitochondrial network. Gene expression profiling revealed the down-regulation of cell proliferation genes whereas genes involved in cell migration and cytokine production were strongly up-regulated by ATP. Functional studies confirmed the inhibitory activity of ATP on proliferation of hMSCs and clonogenic progenitors. Moreover, ATP exerted a chemotactic effect on hMSCs and increased their migration in response to the chemokine CXCL12. Finally, whereas ATP did not affect T-cell inhibitory activity of hMSCs, the nucleotide increased the production of pro-inflammatory cytokines by hMSCs. Thus, our data show that purinergic signaling modulates hMSC functions and point to a role for extracellular nucleotides on hMSCs biology.
Publication Title
Purinergic stimulation of human mesenchymal stem cells potentiates their chemotactic response to CXCL12 and increases the homing capacity and production of proinflammatory cytokines.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
We show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin- CD34-) hematopoietic stem cells (HSCs) from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular caryotyping and quantitative analysis of BCR/ABL transcript demonstrated that about one third of CD34- was leukemic. CML CD34- cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures and cytokines induced CD34 expression on some HSCs, cell cycling, acquisition of clonogenic activity and increased expression of BCR/ABL transcript. CML CD34- cells showed an engraftment rate in immunodeficient mice similar to that of CD34+ cells. Gene expression profiling revealed the down-regulation of cell cycle arrest genes together with genes involved in antigen presentation and processing, while the expression of angiogenic factors was strongly up-regulated when compared to normal counterparts. Flow cytometry analysis confirmed the significant down-regulation of HLA class I and II molecules in CML CD34-cells. Increasing doses of imatinib mesilate (IM) did not affect fusion transcript levels, BCR-ABL kinase activity and the clonogenic efficiency of CML CD34- cells as compared to leukemic CD34+cells.
Publication Title
Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Bitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation.
Publication Title
Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To gain insight into the etiopathogenesis of Multiple sclerosis (MS) we investigated gene expression changes in CD4+ and CD8+ T lymphocytes from monozygotic twins (MZ) discordant for relapsing remitting MS.
Publication Title
CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 112 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In patients with advanced colorectal cancer, leucovorin, fluorouracil, and irinotecan (FOLFIRI) is considered as one of the reference first-line treatments. However, only about half of treated patients respond to this regimen, and there is no clinically useful marker that predicts response. A major clinical challenge is to identify the subset of patients who could benefit from this chemotherapy. We aimed to identify a gene expression profile in primary colon cancer tissue that could predict chemotherapy response. Patients and Methods:- Tumor colon samples from 21 patients with advanced colorectal cancer were analyzed for gene expression profiling using Human Genome GeneChip arrays U133. At the end of the first-line treatment, the best observed response, according to WHO criteria, was used to define the responders and nonresponders. Discriminatory genes were first selected by the significance analysis of microarrays algorithm and the area under the receiver operating characteristic curve. A predictor classifier was then constructed using support vector machines. Finally, leave-one-out cross validation was used to estimate the performance and the accuracy of the output class prediction rule. Results:- We determined a set of 14 predictor genes of response to FOLFIRI. Nine of nine responders (100% specificity) and 11 of 12 nonresponders (92% sensitivity) were classified correctly, for an overall accuracy of 95%. Conclusion:- After validation in an independent cohort of patients, our gene signature could be used as a decision tool to assist oncologists in selecting colorectal cancer patients who could benefit from FOLFIRI chemotherapy, both in the adjuvant and the first-line metastatic setting.
Publication Title
Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan.
Sample Metadata Fields
Specimen part
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