Leukemia is a complex malignancy with hundreds of distinct mutations associated with disease development. Studies have shown that oncogenes cooperate to promote leukemia transformation, however, the downstream effectors of this cooperation are largely unknown.
Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells.
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View SamplesWe generated RNA-seq data to measure transcriptional profiles of twenty hPSC-derived NSC populations, representing distinct regions of the developing human hindbrain and rostral cervical spinal cord. These cells are differentiated using a protocol that induces collinear activation of region-specific HOX genes during exposure to FGF8 and Wnt signaling (Lippmann et al, 2015 PMID:25843047). By transitioning to media containing retinoic acid after varying durations of Wnt signaling, NSCs are generated with unique rostrocaudal identities that uniformly express the neuroectodermal marker Pax6 and form N-cadherin+ rosette structures in vitro. Overall design: The data consist of RNA-seq measurements taken from hPSC-derived NSCs that were exposed to CHIR99021 for differents amount of time (2-72hr) prior to retinoic acid treatment. Each time point is represented in triplicate, with the exception of 48 hours, for which one replicate (48_B1) was filtered due to excessive zero-count genes.
Inferring Regulatory Programs Governing Region Specificity of Neuroepithelial Stem Cells during Early Hindbrain and Spinal Cord Development.
Cell line, Subject
View SamplesIn the normal prostate, most basal and some luminal cells are castration-resistant (CR). The identity of these CR cells and their relation to CR prostate cancer are unresolved. We compared single-cell expression profiles of prostate cells sorted from hormonally nave (HN) and castrated mice. We found both basal and luminal-localized cells, particularly the latter, were molecularly heterogeneous. CR luminal cells and a subset of HN luminal cells exhibited a similar intermediate expression pattern, including high-level expression of multiple prostate stem/progenitor marker genes and androgen receptor gene. We validated LY6D as a marker linking CR luminal cells to luminal progenitors. LY6D+ prostate cells, including LY6D+ luminal cells, were enriched for organoid-forming potential regardless of the presence or absence of androgen. Krt8-based lineage-tracing revealed that LY6D+ CR luminal cells produced LY6D- normal luminal cells upon regeneration, but LY6D+ luminal cancer cells under PTEN-deficiency. Furthermore, prostate cancers originating from CR luminal cells (LY6D+) exhibited a more advanced phenotype than those from HN luminal cells (LY6D+ or LY6D-). Lastly, LY6D amplification/upregulation appear associated with advanced prostate cancer in patient samples. Together, our studies demonstrate LY6D as a novel progenitor marker predictive of lethal CR disease.
Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer.
Sex, Specimen part
View SamplesThe T lymphoma invasion and metastasis inducing protein 1 (TIAM1) is a guanine nucleotide exchange factor (GEF) that activates the small GTPase RAC1 and regulates a plethora of functions such as cell proliferation, migration, apoptosis and polarity. Recently, we demonstrated that TIAM1 shuttles between the cytoplasm and nucleus. To determine the nuclear role of TIAM1, we performed RNA-seq on SW620 cells transfected either with a specific pre-validated siRNA for TIAM1 (siTIAM1) or a negative control siRNA (siNT) and generated a list of TIAM1 differentially expressed genes. GSEA revealed significant enrichment among TIAM1-regulated genes for YAP-associated molecular signature. To investigate the interplay of TIAM1 with YAP/TAZ we used RNA-seq, generated a list of YAP/TAZ differentially expressed genes from SW620 cells transfected either with specific siRNAs for YAP/TAZ or a negative control siRNA and compared it with the siTIAM1 RNA-seq dataset. Interestingly, we found that 50% of the TAZ/YAP regulated genes were also TIAM1 dependent. Overall design: mRNA profiles of control, TIAM1 or YAP/TAZ knockdown SW620 cells were generated from three independent experiments using RNA-seq
TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
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View SamplesAnalysis of the transcriptional response to viral infection in C.elegans.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
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View SamplesAttempt to identify small non-coding RNAs that change in levels as a result of viral infection of C.elegans Overall design: Small non-coding RNA (18-30nt) was extracted from animals either infected with Orsay virus or uninfected as indicated.
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Cell line, Subject
View SamplesThe transition in developmental control from maternal to zygotic gene products marks a critical step in early embryogenesis. Here, we use GRO-seq analysis to map the genome-wide RNA polymerase distribution during the Drosophila maternal to zygotic transition. This analysis unambiguously identifies the zygotic transcriptome, and provides insight into its mechanisms of regulation. Overall design: Two replicates of GRO-seq at each time point.
Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription.
Specimen part, Cell line, Subject, Time
View SamplesYeast cells were grown up in SD media containing all required amino acids. Each strain set was performed in triplicate. One set had no changes, the second set had 1mM methionine supplenting the media for the duration of growth and the third set was exposed to 0.5mM hydrogen peroxide for 15 minutes prior to harvesting
Gcn4 is required for the response to peroxide stress in the yeast Saccharomyces cerevisiae.
Compound
View SamplesWe used an in vivo short hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells in vivo, and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced differentiation via the intracellular kinase, Syk. In contrast, loss of Itgb3 in normal HSPCs did not affect engraftment, reconstitution, or differentiation. Finally, we confirmed that Itgb3 is dispensable for normal hematopoiesis and required for leukemogenesis using an Itgb3 knockout mouse model. Our results establish the significance of the Itgb3 signaling pathway as a potential therapeutic target in AML.
In Vivo RNAi screening identifies a leukemia-specific dependence on integrin beta 3 signaling.
Cell line, Treatment, Time
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