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SRP093731
Mus musculus
15 Downloadable Samples
Illumina HiSeq 2500
Description
Mechanical forces are increasingly recognized to regulate morphogenesis, but how this is accomplished in the context of the multiple tissues present within a developing organ remains unclear. Here we use bioengineered “microfluidic chest cavities” to precisely control the mechanical environment of the fetal lung. We show that transmural pressure controls airway branching morphogenesis and regulates the frequency of airway smooth muscle contraction. Next-generation sequencing analysis shows that lungs held at higher pressure are more mature than lungs held at lower pressure. Timelapse imaging reveals that branching events are synchronized across distant locations within the lung, and are preceded by long-duration waves of airway smooth muscle contraction. Higher transmural pressure decreases the interval between systemic smooth muscle contractions and increases the rate of morphogenesis of the airway epithelium. These data reveal that the mechanical properties of the microenvironment instruct crosstalk between tissues to control the rate of development of the embryonic lung. Overall design: (i) embryonic mouse lungs at E12.5 were cultured under low or high pressure for 48 hours prior to RNA extraction or (ii) embryonic mouse lungs were isolated from pregnant mice at E12.5, E13.5 and E14.5 prior to RNA extraction
Publication Title
Microfluidic chest cavities reveal that transmural pressure controls the rate of lung development.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
RhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
Publication Title
RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sialic acids on vertebrate cell surfaces mediate many biological roles. Altered expression of certain sialic acid types or their linkages can have prognostic significance in human cancer. A classic but unexplained example is enhanced 2-6-sialylation on N-glycans, resulting from over-expression of the Golgi enzyme -galactoside:2-6-sialyltransferase (ST6Gal-I). Previous data supporting a role for the resulting Sia2-3Gal1-4GlcNAc (Sia6LacNAc) structure in tumor biology were based on in vitro studies in transfected carcinoma cells, in which increased Sia6LacNAc on 1-integrins enhanced their binding to ligands, and stimulated cell motility. Here we examine for the first time the in vivo role of the ST6Gal-I enzyme in the growth and differentiation of spontaneous mammary cancers in mice transgenic for an MMTV-promoter-driven polyoma-middle-T antigen, a tumor in which beta1-integrin function is important for tumorigenesis, and in maintaining the proliferative state of tumor cells. Tumors induced in St6gal1 null animals were more differentiated in comparison to those in the wild-type background, both by histological analysis and by protein expression profiles. Furthermore, we show the St6gal1 null tumors have selectively altered expression of genes associated with focal adhesion signaling, and have decreased phosphorylation of FAK, a downstream target of 1-integrins. This first in vivo evidence for a role of ST6Gal-I in tumor progression was confirmed using a novel approach, which conditionally restored St6gal1 in cell lines derived from the null tumors. These findings indicate a role for ST6Gal-I as a mediator of tumor progression, with its expression causing a less differentiated phenotype, via enhanced 1-integrin function.
Publication Title
alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Bortezomib (Velcade) is widely used for the treatment of various human cancers, however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that Bortezomib induces proteasome-independent degradation of TRAF6 protein, but not mRNA, in Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with Bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized Bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in Bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of Bortezomib due to down-regulation of the proteasomal subunit alpha-1 (PSMA1). To uncover the molecular consequences following loss of TRAF6 in MDS/AML cells, we applied gene expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe novel mechanisms by which TRAF6 is regulated through Bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to Bortezomib by controlling PSMA1 expression.
Publication Title
Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The goals of this study were to identify quantitative gene expression differences between whole tumor and tumor-associated macrophages (TAMs) derived from Lewis lung carcinoma (LLC) tumors grown in wild type and PI3Kinase-gamma-null mice. Methods: mRNA profiles of whole tumor or tumor-associated macrophages (CD11b+Gr1- cells) from wild type (WT) or PI3Kinase-gamma-knockout (p110g-/-) mice were generated by single deep read sequencing, in triplicate or quadruplicate, using Illumina HiSeq 2000. The sequence reads that passed quality filters were aligned to mouse transcriptome using the bowtie2 aligner. Gene-level summaries were normalized and analyzed for differential expression using DESeq. Overall design: mRNA profiles of whole tumor and tumor-associated macrophages from WT and p110g-/- mice were generated by deep sequencing in triplicate or quadruplicate using Illumina HiSeq 2000.
Publication Title
PI3Kγ is a molecular switch that controls immune suppression.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: The goals of this study were to identify quantitative gene expression differences between macrophages derived from wild type and PI3Kgamma null macrophages Methods: mRNA profiles of MCSF, IL4 and IFNg/LPS stimulated macrophage wild-type (WT) and PI3Kinase gamma knockout (p110g-/-) mice were generated by single read deep sequencing, in triplicate, using Illumina HiSeq2000. The sequence reads that passed quality filters were aligned to mouse transcriptome using the bowtie2 aligner. Gene-level summaries were normalized and analyzed for differential expression using DESeq. qRT–PCR validation was performed using SYBR Green assays. Conclusions: Our study represents the first detailed analysis of the role of p110g in the control of the macrophage immune response, with biological replicates, generated by RNA-seq technology. Overall design: mRNA profiles of wild type (WT) and p110g-/- macrophages were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
Publication Title
PI3Kγ is a molecular switch that controls immune suppression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Purpose: To use RNA-Seq analysis of endothelial cell in various Notch1 alllels in order to determine transcrptional differencesas a consequence of Notch dose. Methods: Using a FACS sorting we generated high-throughput RNA-SEQ data of endothelials in various Notch1 alleles during development Results: Notch1 dose can alter gene expression in a subset of endothelial genes Overall design: RNA-Seq was performed on endothelial cells isolated at e9.5 from embryos with various Notch1 alleles including N1+/+, N1+/-, N1+/vg, N112/vg, N112/-
Publication Title
The intracellular domains of Notch1 and Notch2 are functionally equivalent during development and carcinogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Hordeum vulgare
- 35 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Drought tolerance is a key trait for increasing and stabilizing barley productivity in dry areas worldwide. Identification of the genes responsible for drought tolerance in barley (Hordeum vulgare L.) will facilitate understanding of the molecular mechanisms of drought tolerance, and also genetic improvement of barley through marker-assisted selection or gene transformation. To monitor the changes in gene expression at transcription levels in barley leaves during the reproductive stage under drought conditions, the 22K Affymetrix Barley 1 microarray was used to screen two drought-tolerant barley genotypes, Martin and Hordeum spontaneum 41-1 (HS41-1), and one drought-sensitive genotype Moroc9-75. Seventeen genes were expressed exclusively in the two drought-tolerant genotypes under drought stress, and their encoded proteins may play significant roles in enhancing drought tolerance through controlling stomatal closure via carbon metabolism (NADP malic enzyme (NADP-ME) and pyruvate dehydrogenase (PDH), synthesizing the osmoprotectant glycine-betaine (C-4 sterol methyl oxidase (CSMO), generating protectants against reactive-oxygen-species scavenging (aldehyde dehydrogenase (ALDH), ascorbate-dependant oxidoreductase (ADOR), and stabilizing membranes and proteins (heat-shock protein 17.8 (HSP17.8) and dehydrin 3 (DHN3). Moreover, 17 genes were abundantly expressed in Martin and HS41-1 compared with Moroc9-75 under both drought and control conditions. These genes were likely constitutively expressed in drought-tolerant genotypes. Among them, 7 known annotated genes might enhance drought tolerance through signaling (such as calcium-dependent protein kinase (CDPK) and membrane steroid binding protein (MSBP), anti-senescence (G2 pea dark accumulated protein GDA2) and detoxification (glutathione S-transferase (GST) pathways. In addition, 18 genes, including those encoding l-pyrroline-5-carboxylate synthetase (P5CS), protein phosphatase 2C-like protein (PP2C) and several chaperones, were differentially expressed in all genotypes under drought; thus, they were more likely general drought-responsive genes in barley. These results could provide new insights into further understanding of drought-tolerance mechanisms in barley.
Publication Title
Differentially expressed genes between drought-tolerant and drought-sensitive barley genotypes in response to drought stress during the reproductive stage.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
In this study we investigated the changes in mRNA expression upon treatment of SH-SY5Y cells to 10M cisplatin for 72h.
Publication Title
Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hematopoietic stem cell function and survival depend on c-Myc and N-Myc activity.
Sample Metadata Fields
Age, Specimen part
View Samples