Mouse hair follicles (HFs) undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). During the rest phase, the HF-SCs remain quiescent due to extrinsic inhibitory signals within the niche. As activating cues accumulate, HF-SCs become activated, proliferate, and grow downward to form transient-amplifying matrix progenitor cells. We used microarrays to detect the relative levels of global gene expression underlying the states of hair follicle stem cells and their transient-amplifying progeny before differentiation.
Genome-wide maps of histone modifications unwind in vivo chromatin states of the hair follicle lineage.
Sex, Specimen part
View SamplesTo dissect molecular pathways regulated by TRIB2 in T-ALL, we performed microarray gene expression profiling in the TAL1-positive T-ALL cells (Jurkat) after TRIB2 knockdown.
TRIB2 reinforces the oncogenic transcriptional program controlled by the TAL1 complex in T-cell acute lymphoblastic leukemia.
Specimen part, Cell line
View SamplesMLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer.
Aberrant chromatin at genes encoding stem cell regulators in human mixed-lineage leukemia.
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Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.
Disease, Cell line
View SamplesThe oncogenic transcription factor TAL1/SCL is aberrantly overexpressed in over 40% of cases of T-cell acute lymphoblastic leukemia (T-ALL), emphasizing the importance of the TAL1-regulated transcriptional program in the molecular pathogenesis of T-ALL. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, GATA3, ETS1 and RUNX1 in T-ALL cells. We find that TAL1 forms an interconnected auto-regulatory loop with its partners, which contributes to the sustained upregulation of its direct target genes. Importantly, we also find the MYB oncogenic transcription factor is directly activated by the TAL1 complex and positively regulates many of the same target genes, thus forming a feed-forward positive regulatory loop that further promotes the TAL1-regulated oncogenic program.
Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were treated with either 100mg/kg baclofen or 0.5% methylcellulose alone by oral gavage for 1 or 5 days.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesMice were dosed with 2-BE (900mg/kg) or vehicle by oral gavage and sacrificied either after 4 hours of a single dose or after 7 days of daily dosing.
The role of hypoxia in 2-butoxyethanol-induced hemangiosarcoma.
Specimen part, Treatment, Time
View SamplesAnalysis of mobilized peripheral blood CD34+ cells from a healthy volunteer under erythroid differentiation conditions with and without stimulation to the BMP or Wnt signaling pathways. For erythroid differentiation, expanded CD34+ cells were placed in Stemspan SFEM medium supplemented with 2% pen/strep, 20ng/ml SCF, 1U/ml Epo, 5ng/ml IL3, 2uM dexamethasone, and 1uM beta-estradiol. Arrays were performed 2 hours after addition of cytokines. For signaling pathway stimulation, cells were exposed to 0.5uM BIO (a GSK3 inhibitor) for Wnt pathway activation, 25ng/ml rhBMP4 for BMP pathway activation, or vehicle control for 2 hours. Three biological replicates were performed per treatment group.
Lineage regulators direct BMP and Wnt pathways to cell-specific programs during differentiation and regeneration.
Specimen part, Disease
View SamplesIn the present study, we sought to understand the impact of obesity/metabolic disease (high-fat induced) on spinal cord injury (SCI) by examining transcriptome. Adult, male Long Evans rats received either thoracic level contusion of the spinal cord or sham laminectomy and then were allowed to recover on normal rat chow for 4 weeks and further on HFD for an additional 8 weeks. Spinal cord tissues harvested from the rats were processed for Affymetrix microarray and further transcriptomic analysis.
Chronic spinal cord changes in a high-fat diet-fed male rat model of thoracic spinal contusion.
Sex, Specimen part
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