Human microvascular endothelial cells (HMVEC) treated with vascular endothelial growth factor (VEGF), Antrhax Edema Toxin (ET), or the Epac activator, 8-pCPT-2'-O-Me-cAMP (8CPT)
Anthrax edema toxin inhibits endothelial cell chemotaxis via Epac and Rap1.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.
Specimen part, Cell line
View SamplesIt has been known for some time that muscle repair potential becomes increasingly compromised with advancing age, and that this age-related defect is associated with reduced activity of muscle satellite cells and with the presence of chronic, low grade inflammation in the muscle. Working from the hypothesis that a heightened inflammatory tone in aged muscle could contribute to poor regenerative capacity, we developed genetic systems to inducibly alter inflammatory gene expression in satellite cells or muscle fibers by modulation of the activity of nuclear factor B (NF-B), a master transcriptional regulator of inflammation whose activity is upregulated in many cell types and tissues with age. These studies revealed that activation of NF-B activity in muscle fibers, but not in satellite cells, drives muscle dysfunction and that lifelong inhibition of NF-B activity in myofibers preserves muscle regenerative potential with aging via cell-non-autonomous effects on satellite cell function. Further analysis of differential gene expression in muscles with varying NF-B activity identified a secreted phospholipase (PLA2G5) as a myofiber-expressed NF-B-regulated gene that governs muscle regenerative capacity with age. Together, these data suggest a model in which NF-B activation in muscle fibers increases PLA2G5 expression and drives the impairment in regenerative function characteristic of aged muscle. Importantly, inhibition of NF-B function reverses this impairment, suggesting that FDA-approved drugs, like salsalate, a prodrug form of sodium salicylate, may provide new therapeutic avenues for elderly patients with reduced capacity to recover effectively from muscle injury.
Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function.
Age
View SamplesRKIP regulates human breast tumor metastasis. We use gene expression array analysis to identify genes regulated by RKIP in human breast cancer cells.
RKIP and HMGA2 regulate breast tumor survival and metastasis through lysyl oxidase and syndecan-2.
Specimen part, Cell line
View SamplesPatient selection and specimen collection. Thirty-six freshly frozen tumor samples were prospectively collected from patients undergoing surgery or biopsy for HNSCC at the University of North Carolina (UNC) at Chapel Hill (21 patients) and Vanderbilt University (15 patients). All tissues were snap-frozen in liquid nitrogen within 30 minutes of surgical resection or biopsy, and kept at -80oC until further processing. All patients consented to participation in this study under protocols approved by IRB at the two institutions.
A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
No sample metadata fields
View SamplesHMGA2, Tet1 and HOXA9 are all regulated human breast tumorigenesis. We use gene expression array analysis to identify and compare the genes regulated by HMGA2, Tet1 and/or HOXA9 in human breast cancer cells.
HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis.
Specimen part, Cell line
View SamplesProtein Kinase C alpha (PKC) is a critical mediator of cell signaling and cancer growth. We show that PKC inhibitors decrease proliferation in squamous cell carcinoma of the head and neck (SCCHN) cells and abrogate growth of SCCHN tumors in mouse xenografts. Analysis of gene expression arrays reveals that PKC regulates cell cycle genes required for DNA synthesis. In particular, PKC increases cyclin E protein expression, cyclinE/cdk2 complex formation, and transcription of cyclin E and E2F target genes. Consistent with this mechanism, expression of cyclin E rescues the block in DNA synthesis caused by PKC inhibition. In SCCHN tissue, PKC and cyclin E expression increase progressively from normal and dysplastic to malignant human head and neck tissue. Furthermore, PKC expression correlates with poor prognosis in SCCHN. These results demonstrate that PKC regulates growth by stimulating DNA synthesis through cyclin E and E2F and identify PKC as a therapeutic target that is highly expressed in aggressive SCCHN.
A feed-forward loop involving protein kinase Calpha and microRNAs regulates tumor cell cycle.
No sample metadata fields
View SamplesIn this study, we investigated signaling pathways in Skeletal muscle precursors that are altered with aging and age-related deficits in muscle regenerative potential. We performed fluorescence activated cell sorting (FACS) to obtain highly purified skeletal muscle satellite cells from young, middle-aged and old mice.
Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.
Specimen part
View SamplesTranscriptomic analysis of ICM and TE from in vivo-derived equine blastocysts using Illumina sequencing technology Overall design: RNA was extracted from individual equine blastocyst ICM and TE (Arcturus Picopure), cDNA was synthesized and amplified (Nugen Ovation V2) and indexed libraries were created for sequencing (TruSeq DNA V1)
RNA-seq transcriptome profiling of equine inner cell mass and trophectoderm.
Specimen part, Subject
View SamplesAlthough liganded nuclear receptors have been established to regulate RNA polymerase II (Pol II)-dependent transcription units, their role in regulating Pol III-transcribed DNA repeats remains largely unknown. Here we report that ~2-3% of the ~100,000-200,000 total human DR2 Alu repeats located in proximity to activated Pol II transcription units are activated by the retinoic acid receptor (RAR) in human embryonic stem cells to generate Pol III-dependent RNAs. These transcripts are processed, initially in a DICER-dependent fashion, into small RNAs (~28-65 nt) referred to as repeat-induced RNAs that cause the degradation of a subset of crucial stem-cell mRNAs, including Nanog mRNA, which modulate exit from the proliferative stem-cell state. This regulation requires AGO3-dependent accumulation of processed DR2 Alu transcripts and the subsequent recruitment of AGO3-associated decapping complexes to the target mRNA. In this way, the RAR-dependent and Pol III-dependent DR2 Alu transcriptional events in stem cells functionally complement the Pol II-dependent neuronal transcriptional program. Overall design: RNA-sequencing of polyA selected RNA molecules in NTera2/D1 cells and Global Run On (GRO) assay followed by high throughput sequencing (GRO-seq).
DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation.
Specimen part, Treatment, Subject
View Samples