Expression data from this experiment is part of a larger project aimed at defining the individual effects and synergistic effects of ROCK inhibitor Y-27632 and conditioned media from irradiated J2 cells when applied to epithelial cells. This data set consists of four individual samples, each of which are total RNA collected from human foreskin keratinocyte cells, either grown in F medium (control), treated with Y-27632, grown in conditioned medium (as described in associated publication), or both treatments.
Multifactorial analysis of conditional reprogramming of human keratinocytes.
Specimen part, Treatment
View SamplesHuman tumors often contain slowly proliferating cancer cells that resist treatment but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating G0-like progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur.
Asymmetric cancer cell division regulated by AKT.
Specimen part, Cell line
View SamplesRift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored. Overall design: The study included triplicate samples of HSAEC cells infected with Mock, MP12, or ZH548 strains of RVFV, and collected at 3, 9, and 18 hourse post-infection. There are a total of 27 samples.
Phosphoproteomic analysis reveals Smad protein family activation following Rift Valley fever virus infection.
Specimen part, Subject, Time
View SamplesComparison between cell lines from 9 different cancer tissue of origin types (Breast, Central Nervous System, Colon, Leukemia, Melanoma, Non-Small Cell Lung, Ovarian, Prostate, Renal) from NCI-60 panel
Transcript and protein expression profiles of the NCI-60 cancer cell panel: an integromic microarray study.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesNotch1 signaling is absolutely essential for steady-state thymic lymphopoiesis, but the role of other Notch receptors, and their potential overlap with the function of Notch1, remains unclear. Here we show that like Notch1, Notch3 is differentially expressed by progenitor thymocytes, peaking at the DN3 progenitor stage. Using mice carrying a gene-trapped allele, we show that thymic cellularity is slightly reduced in the absence of Notch3, although progression through the defined sequence of TCR- development is normal, as are NKT and TCR cell production.
Nonoverlapping functions for Notch1 and Notch3 during murine steady-state thymic lymphopoiesis.
Sex, Age, Specimen part
View SamplesExercise attenuates the development of chronic non-communicable diseases (NCDs). Gene signaling pathway analysis offers an opportunity to discover if electrically induced muscle exercise regulates key pathways among people living with spinal cord injury (SCI). We examined short-term and long-term durations of electrically induced skeletal muscle exercise on complex gene signaling pathways, specific gene regulation, and epigenetic tagging of PGC1a, a major transcription factor in skeletal muscle of men with SCI. After short or long-term electrically induced exercise training, participants underwent biopsies of the trained and untrained muscles. RNA was hybridized to an exon microarray and analyzed using a gene set enrichment analysis. We discovered that long-term exercise training regulated the Reactome gene sets for Metabolism (38 gene sets), Cell Cycle (36 gene sets), Disease (27 gene sets), Gene Expression and Transcription (22 gene sets), Organelle Biogenesis (4 gene sets), Cellular Response to Stimuli (8 gene sets), Immune System (8 gene sets), Vesicle Mediated Transport (4 gene sets), and Transport of Small Molecules (3 gene sets). Specific gene expression included: Oxidative catabolism of glucose including PDHB (p<0.001), PDHX (p<0.001), MPC1 (p<0.009), and MPC2 (p<0.007); Oxidative phosphorylation genes including SDHA (p<0.006), SDHB (p<0.001), NDUFB1 (p<0.002), NDUFA2 (p<0.001); Transcription Genes including PGC1α (p<0.030) and PRKAB2 (p<0.011); Hypertrophy gene MSTN (p<0.001); and the Myokine generating FNDC5 gene (p<0.008). Long-term electrically induced exercise de-methylated the major transcription factor, PGC1a. Taken together, these findings support that long term electrically induced muscle activity regulates key pathways associated with muscle health and systemic metabolism.
Impact of short- and long-term electrically induced muscle exercise on gene signaling pathways, gene expression, and PGC1a methylation in men with spinal cord injury.
Sex, Specimen part, Disease
View SamplesExpression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not -catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking -catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation.
The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.
Cell line
View SamplesThe molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors.
The BAF complex interacts with Pax6 in adult neural progenitors to establish a neurogenic cross-regulatory transcriptional network.
Sex, Age, Specimen part
View SamplesInteraction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cell identity regulators link development and stress responses in the Arabidopsis root.
Age, Specimen part, Treatment
View Samples