Aging is associated with a decline in hippocampal mediated learning and memory, a process wich can be ameliorated by dietary (caloric) restriction. We used Affymetrix gene expression analysis to monitor changes in three regions of the hippocampus (CA1, CA3, DG) of middle aged (18 months) and old (28 month) rats that were exposed to dietary restriction. Old rats were determined to be good performers (GP) or poor performers (PP) in behavioral tests to assess thier hippocampal function.
Gene expression in the hippocampus: regionally specific effects of aging and caloric restriction.
Age, Specimen part
View SamplesMicroRNAs (miRNAs) play important roles in modulating gene expression at the post-transcriptional level. In postnatal oligodendrocytes, the miRNA expression profile -microRNAome - consists of 98 miRNAs whose expression dynamically changes during the transition from A2B5+ oligodendrocyte progenitor cells to premyelinating GalC+ cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is down-regulated during oligodendrocyte differentiation. In addition, miR-9 expression levels inversely correlate with the expression of its predicted targets, among which is the peripheral myelin protein, PMP22. PMP22 mRNA but not protein is detectable in oligodendrocytes, while Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3 untranslated region of PMP22 and down-regulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome.
Identification of dynamically regulated microRNA and mRNA networks in developing oligodendrocytes.
No sample metadata fields
View SamplesGene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Cell line, Treatment
View SamplesThe study consist of patients who presented at Memorial Sloan-Kettering Cancer Center with a colonic neoplasm between 1992 and 2004. Biological specimens used in this study include primary colon adenocarcinomas, adenomas, metastasis and corresponding normal mucosae.
Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer.
Sex, Age, Specimen part, Cell line, Subject
View SamplesRNA expression data was generated as part of a colon cancer study. Samples were obtained from patients, including primary colon cancer, polyps, metastases, and matched normal mucosa (obtained from the margins of the resection). The RNA was extracted from tissue samples obtained from resections and hybridized to Affymetrix HG-U133 arrays. RNA expression data was also obtained for a few cell lines.
Association of survival and disease progression with chromosomal instability: a genomic exploration of colorectal cancer.
Specimen part, Disease, Disease stage, Cell line
View SamplesAnalysis of lineage depleted human cord blood cells sequentially transduced with retro- (BCR-ABL1) and lentiviral (Ik6) vectors and the corresponding controls. Results provide important informations on the collaboration of BCR-ABL1 and Ik6 in human hematopoietic cells.
Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts.
Specimen part
View SamplesSMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target.
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.
Specimen part, Cell line
View SamplesNext-generation sequencing (NGS) technology applications like RNA-sequencing (RNA-seq) have dramatically expanded the potential for novel genomics discoveries, but the proliferation of various platforms and protocols for RNA-seq has created a need for reference data sets to help gauge the performance characteristics of these disparate methods. Here we describe the results of the ABRF-NGS Study on RNA-seq, which leverages replicate experiments across multiple sites using two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). These results show high (R2 >0.9) intra-platform consistency across test sites, high inter-platform concordance (R2 >0.8) for transcriptome profiling, and a large set of novel splice junctions observed across all platforms. Also, we observe that protocols using ribosomal RNA depletion can both salvage degraded RNA samples and also be readily compared to polyA-enriched fractions. These data provide a broad foundation for standardization, evaluation and improvement of RNA-seq methods. Overall design: Two reference RNA standards tested with four protocols (polyA selected, ribo-depleted, size selected, and degraded RNA), and examined across five NGS platforms (Illumina’s HiSeqs, Life Technologies’ Personal Genome Machine and Proton, Roche 454 GS FLX, and Pacific Biosciences RS). Please note that the samples were named following the ABRF-Platform-Site-Sample-Replicate# format. For example, ABRF-454-CNL-A-1 means Sample A was run on 454 platform at Cornell and this is the first replicate, and ABRF-454-CNL-A-2 means the same exact sample was ran with same machine at same location and is 2nd replicate.
RNA-seq of human reference RNA samples using a thermostable group II intron reverse transcriptase.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
No sample metadata fields
View SamplesIn addition to the estrogen responsive element (ERE)-dependent gene expression, E2-ERbeta regulates transcription through functional interactions with transfactors bound to their cognate regulatory elements on DNA, hence the ERE-independent signaling pathway. However, the relative importance of the ERE-independent pathway in E2-ERbeta signaling is unclear. Our studies in infected ER-negative cell models with an ERbeta mutant (ERbetaDBD) that functions exclusively at the ERE-independent pathway demonstrated that genomic responses assessed by microarrays from the ERE-independent pathway to E2-ERbeta are not sufficient to alter cellular growth, death or motility. These findings suggest that the ERE-dependent pathway is the canonical E2-ERbeta signaling in model cell lines.
Genomic responses from the estrogen-responsive element-dependent signaling pathway mediated by estrogen receptor alpha are required to elicit cellular alterations.
No sample metadata fields
View Samples