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Mus musculus
63 Downloadable Samples
Illumina HiSeq 2500
Description
Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons of the arcuate nucleus of the hypothalamus (ARC) are oppositely regulated by caloric depletion and coordinately stimulate and inhibit homeostatic satiety, respectively. This bimodality is principally underscored by the antagonistic actions of these ligands at downstream melanocortin-4 receptors (MC4R) in the paraventricular nucleus of the hypothalamus (PVH). Although this population is critical to energy balance, the underlying neural circuitry remains unknown. Using mice expressing Cre recombinase in MC4R neurons, we demonstrate bidirectional control of feeding following real-time activation and inhibition of PVH(MC4R) neurons and further identify these cells as a functional exponent of ARC(AgRP) neuron-driven hunger. Moreover, we reveal this function to be mediated by a PVH(MC4R)?lateral parabrachial nucleus (LPBN) pathway. Activation of this circuit encodes positive valence, but only in calorically depleted mice. Thus, the satiating and appetitive nature of PVH(MC4R)?LPBN neurons supports the principles of drive reduction and highlights this circuit as a promising target for antiobesity drug development. Overall design: Single-neuron mRNA-seq was performed on fluorescently-labeled or -unlabeled cells that were manually isolated from dissociated adult mouse paraventricular and arcuate hypothalamus: Mc4r-2a-Cre::L10-GFP+ or Mc4r-2a-Cre::AAV-XFP+ or Mc4r-2a-Cre::AAV-XFP-negative PVH neurons; Agrp-IRES-Cre::L10-GFP+ ARC neurons; Pomc-hrGFP+ ARC neurons; and vGLUT2-IRES-Cre::AAV-XFP+ ARC neurons Note: Raw files unavailable for samples GSM2413312 GSM2413313 GSM2413314 GSM2413346 GSM2413347
Publication Title
A neural basis for melanocortin-4 receptor-regulated appetite.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Analyses of gene expression by RNA-Seq in mouse E14.5 fetal liver burst-forming unit erythroid (BFU-E) cells untreated or treated by dexamethasone (DEX) with or without PPARa agonist GW7647. Overall design: RNA-Seq was performed on enriched populations of mouse BFU-E isolated from E14.5 fetal liver, as well as BFU-E enriched cells treated with Dex ± GW7647.
Publication Title
PPAR-α and glucocorticoid receptor synergize to promote erythroid progenitor self-renewal.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2000
Description
Erythroid progenitor BFU-Es are so-named based on their ability to generate in methylcellulose culture large colonies of erythroid cells that consist of “bursts” of smaller erythroid colonies derived from the later CFU-E Epo- dependent progenitors. “Early” BFU-E cells forming large BFU-E colonies presumably have higher capacities for self-renewal than do those forming small BFU-E colonies. In order to understand the mechanism underlying this heterogeneity, we conducted single cell transcriptome analysis on BFU-E cells purified from mouse embryos. Our analyses showed that there are two principal subgroups of mouse BFU-E cells and that the type III TGFß receptor (TßRIII) is a potential marker that distinguishes “early” and “late” BFU-Es. Expression of TßRIII is correlated with that of GATA1, a gene encoding an erythroid transcription factor induced during the BFU-E to CFU-E transition. The mouse and human BFU-E sub populations (TßRIII10%lo) expressing the 10% lowest amount of surface TßRIII are indeed enriched for early BFU-Es, and are significantly more responsive to glucocorticoid stimulation, which promotes BFU-E self-renewal, as compared to the total BFU-E population. The TßRIII10%lo BFU-E subpopulation presumably represents earlier BFU-Es with maximal capacity for self-renewal. Consistent with this notion, signaling by the TGFß receptor kinases RI and RII increases during the transition from early (TßRIII10%lo) to late (TßRIII10%hi) BFU-Es and then decreases in CFU-E cells. Blocking TGF-ß signaling by receptor kinase inhibitors increase TßRIII10%lo BFU-E cell self-renewal and increases total erythroblast production, suggesting the use of this type of drug in treating Epo unresponsive anemias. Overall design: Discovery of BFU-E subpopulations
Publication Title
TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- NextSeq 500
Description
The regulatory mechanisms that shapes the hepatic zonation is not well understood. In addition, the concept and significance of of hepatic zonation is well established in rodens, however, its relavence to human liver biology remain elusive. We conducted a comprehensive transcriptome analysis of each zonation within normal human liver vis Laser Capture Microdissection approach. Here, we report a poly A RNA sequencing data of the individual zone of liver tissue as well as the whole liver of the corresponding subjects. Overall design: The RNA samples were collected from each zone within hepatic lobule by a Laser Captured Microdissection approach. This study examined the gene expression profile in each zone of the normal human liver.
Publication Title
Dual modulation of human hepatic zonation via canonical and non-canonical Wnt pathways.
Sample Metadata Fields
Sex, Subject
View Samples
GSE11407- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The purpose of this study was to characterize the gene expression profile of MDA-MB-231 breast cancer cells treated with various SCFA-hexosamine analogs to better understand the role of various modifications to this scaffold.
Publication Title
Hexosamine template. A platform for modulating gene expression and for sugar-based drug discovery.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 93 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 93 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
mRNA expression profile of cultured Breast Cancer cell line measured by Affymetrix microarrays
Publication Title
MCL-1 Is a Key Determinant of Breast Cancer Cell Survival: Validation of MCL-1 Dependency Utilizing a Highly Selective Small Molecule Inhibitor.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study addresses long-term effects of clinically relevant regimens of radiation in human glioma stem cells. Our investigations reveal a strikingly diverse spectrum of changes in cell behavior, gene expression patterns and tumor-propagating capacities evoked by radiation in different types of glioma stem cells. Evidence is provided that degree of cellular plasticity but not the propensity to self-renew is an important factor influencing radiation-induced changes in the tumor-propagating capacity of glioma stem cells. Gene expression analyses indicate that paralell transcriptomic responses to radiation underlie similarity of clinically relevant cellular outcomes such as the ability to promote tumor growth after radiation. Our findings underscore the importance of longitudinal characterizations of molecular and cellular responses evoked by cytotoxic treatrments in glioma stem cells.
Publication Title
Diversity of Clinically Relevant Outcomes Resulting from Hypofractionated Radiation in Human Glioma Stem Cells Mirrors Distinct Patterns of Transcriptomic Changes.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We showed different function of monocyte derived cells in the lamina propria of the colon under steady state and inflammatory conditions.
Publication Title
Ly6C hi monocytes in the inflamed colon give rise to proinflammatory effector cells and migratory antigen-presenting cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epigenetic events, including covalent post-translational modification of histones, have frequently been demonstrated to play critical roles in tumor development and progression. The transcriptional coactivator, p300/CBP, possesses both histone acetyltransferase (HAT) activity as well as scaffolding properties that directly influence transcriptional activation of targeted genes. We have used a recently reported small molecule inhibitor of p300 HAT activity, C646, to explore the specific contribution of p300/CBP HAT activity to tumor development and progression. We find that C646 inhibits the growth of lineage-specific tumor cell lines including human melanomas through direct transcriptional regulation of cell cycle regulatory proteins. Further evaluation of the p300 HAT transcriptome in human melanoma cells using comprehensive gene expression profiling reveals that p300 HAT activity globally promotes cell cycle progression, nucleosome assembly, and the DNA damage checkpoint through direct transcriptional regulatory mechanisms. Additionally, C646 promotes sensitivity to DNA damaging agents leading to enhanced apoptosis of melanoma cells following combination treatment with cisplatin. Together our data suggest that p300 HAT activity regulates critical growth regulatory pathways in tumors and may serve as a novel therapeutic target for melanoma and other malignancies by promoting cellular responses to DNA damaging agents.
Publication Title
Selective inhibition of p300 HAT blocks cell cycle progression, induces cellular senescence, and inhibits the DNA damage response in melanoma cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples