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SRP063833
Mus musculus
7 Downloadable Samples
Illumina HiSeq 2000
Description
The Mdm2 oncoprotein ubiquitinates and antagonizes p53 but may also carry out p53-independent functions. Here we report that Mdm2 is required for the efficient generation of induced pluripotent stem cells (iPSCs) from murine embryonic fibroblasts, in the absence of p53. Similarly, Mdm2 depletion in the context of p53 deficiency also promoted the differentiation of human mesenchymal stem cells and diminished clonogenic survival of cancer cells. Most of the Mdm2-controlled genes also responded to the inactivation of the Polycomb Repressor Complex 2 (PRC2) and its catalytic component EZH2. Mdm2 physically associated with EZH2 on chromatin, enhancing the trimethylation of Histone 3 at lysine 27 and the ubiquitination of Histone 2A at lysine 119 (H2AK119) at its target genes. Removing Mdm2 simultaneously with the H2AK119 E3 ligase Ring1B/RNF2 further induced these genes and synthetically arrested cell proliferation. In conclusion, Mdm2 supports the Polycomb-mediated repression of lineage specific genes independent of p53. Overall design: Expression profiling by high throughput sequencing of p53 ko MEFs, p53Mdm2 ko MEFs, p53ko Mdm2 C462A ki MEFs.
Publication Title
MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Comparative RNA seq analysis of WT and global p73KO Mouse Tracheal Epithelial Cell (MTECs) during the course of their differentiation (Air-Liquid Interface ALI D0, D4, D7, D14) aimed to determine the role of p73 in motile multiciliogenesis. Overall design: Three independent biological replicates of murine primary airway epithelial cell cultures (MTECs) from wild type and global p73KO mice were differentiated under air-liquid interface (ALI) conditions and harvested at Day 0, Day 4 , Day 7 and Day 14 post ALI.
Publication Title
TAp73 is a central transcriptional regulator of airway multiciliogenesis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq1500
Description
Direct conversion of somatic cells into neural stem cells (NSCs) by defined factors holds great promise for mechanistic studies, drug screening, and potential cell therapies for different neurodegenerative diseases. Here, we report that a single zinc-finger transcription factor, Zfp521, is sufficient for direct conversion of human fibroblasts into long-term self-renewable and multipotent NSCs. In vitro, Zfp521-induced NSCs maintained their characteristics in the absence of exogenous factor expression and exhibited morphological, molecular, developmental, and functional properties that were similar to control NSCs. Additionally, the single seeded induced NSCs were able to form NSC colonies with efficiency comparable to control NSCs and expressed NSC markers. The converted cells were capable of surviving, migrating and attaining neural phenotypes after transplantation into neonatal mouse- and adult rat brains, without forming tumors. Moreover, the Zfp521-induced NSCs predominantly expressed rostral genes. Our results suggest a facilitated approach for establishing human NSCs through Zfp521-driven conversion of fibroblasts. Overall design: RNA-Seq of 3 replicates each of iNSC, WT-NSC, and HNF
Publication Title
Conversion of Human Fibroblasts to Stably Self-Renewing Neural Stem Cells with a Single Zinc-Finger Transcription Factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
gene expression profiling by RNA-seq in THP-1 cells treated with 1,25(OH)2D3 for 2.5-24 h Overall design: three independent experiments of 1,25(OH)2D3 time course in THP-1 cells
Publication Title
Epigenome-wide effects of vitamin D and their impact on the transcriptome of human monocytes involve CTCF.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BRG1, an ATPase catalytic subunit of the SWI/SNF chromatin remodeling complex, has been identified as a tumor suppressor protein, as it has been shown to play a role in Nucleotide Excision Repair (NER) of CPDs, suppress apoptosis, and restore checkpoint deficiency, in response to UV exposure. Although BRG1 has been shown to regulate transcription of some genes that are instrumental in proper DNA damage repair and cell cycle maintenance in response to UV, its role in transcriptional regulation of the whole genome in response to UV has not yet been elucidated. With whole genome expression profiling in SW13 cells, we show that upon UV induction, BRG1 regulates transcriptional expression of many genes involved in cell stress response. Additionally, our results also highlight BRG1s general role as a master regulator of the genome, as it transcriptionally regulates approximately 4.8% of the human genome, including expression of genes involved in many pathways.
Publication Title
Whole genome expression profiling shows that BRG1 transcriptionally regulates UV inducible genes and other novel targets in human cells.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 11 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
While the close relationship between BRs and auxin has been widely reported, the molecular mechanism for combinatorial control of shared target genes has remained elusive. In this work, we demonstrate that BRs synergistically increase seedling sensitivity to auxin and show that combined treatment with both hormones can increase the magnitude and duration of gene expression. arf2 mutants are less sensitive to changes in endogenous BR levels, while a large number of genes affected in an arf2 background are returned to near wild-type levels by altering BR biosynthesis. Together, these data suggest a model where BIN2 increases expression of auxin-induced genes by directly inactivating repressor ARFs, leading to synergistic increases in transcription.
Publication Title
Integration of auxin and brassinosteroid pathways by Auxin Response Factor 2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. Overall design: mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).
Publication Title
Expression Profiling of Macrophages Reveals Multiple Populations with Distinct Biological Roles in an Immunocompetent Orthotopic Model of Lung Cancer.
Sample Metadata Fields
Cell line, Subject
View Samples- Populus trichocarpa
- 18 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We studied the changes that occur in gene transcription during seasonal senescence in Populus trichocarpa pioneer leaves and fine roots. Plant senescence is a strictly regulated physiological process that allows relocating of valuable nutrients from senescent tissues before death. It might be induced by internal or external factors and among them, phytohormones play an undoubtedly significant role. Senescence was extensively studied in leaves, but the aging of other ephemeral organs, located underground, and its drivers are still poorly understood. We focused on collective results to fill in the knowledge gap about senescence of fine, absorptive roots and leaves in order to check if there are universal mechanisms involved during plant organ senescence. Transcriptional profiling was conducted with the use of microarrays to identify genes involved in developmental PCD. Samples were collected three times during a growth season. The first collection was considered as a control and was collected in early summer (July 7–15) when leaves and the root system were fully developed and functional. The second group of leaf and root samples were harvested in early autumn (October 1–7) when chlorophyll levels in leaves had decreased by approximately 40% and when fine roots had changed in color from white to brown. The third group of samples were harvested in the middle of autumn (November 2–9) when chlorophyll levels in leaves decreased by approximately 65% and fine roots were dark brown or black color. Our results reveal the important role of phytohormones in regulating the senescence of both studied organs. The transcriptomic analyses showed significant changes in gene expression that are associated with phytohormones, especially with ABA and jasmonates. We conclude that phytohormonal regulation of senescence in roots and leaves is organ-specific. In roots, phytohormones are involved indirectly in regulation of senescence by increasing tolerance for cold or resistance for pathogens, whereas such correlation was not observed in leaves.
Publication Title
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (<i>Populus trichocarpa</i>).
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Search for transcripts encoding secreted proteins whose expression are highly induced after phlebotomy.
Publication Title
Identification of erythroferrone as an erythroid regulator of iron metabolism.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Mus musculus
- 31 Downloadable Samples
- Illumina HiSeq 2000
Description
Pitx1, critical regulator of a limited hindlimb-specific gene network, targets the limb development program common to both fore- and hindlimbs in order to implement hindlimb-specific limb morphology. Overall design: The gene regulatory networks governing forelimb vs. hindlimb development in mouse were investigated using expressing profiling of morphologically stage-matched e10.5 forelimbs and e11.0 hindlimbs, ChIPseq of chromatin marks, and ChIPseq of limb-specific transcription factors Pitx1 and Tbx5. The makeup of the Pitx1-directed components of the hindlimb gene network were investigated using expression profiling of Pitx1 null hindlimbs at two stages (e11.0 and e11.5).
Publication Title
Regulatory integration of Hox factor activity with T-box factors in limb development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples