During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates. Overall design: RNA samples from Chx10-ESC-derived MNs were prepared for sequencing according to the Illumina protocol, and sequenced on the Illumina HiSeq 2000. We will then compare the transcriptome changes between -Dox (no Chx10) and +Dox (Chx10) in order to identify genes rregulated by Chx10.
Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes.
Specimen part, Treatment, Subject
View SamplesThe recent interest in the role of bone marrow derived endothelial progenitor cells in the benefits of estrogen on cardiovascular health brought us to evaluate if estrogen could affect cardiac repair more broadly by regulating biological processes involved in the functional organization of the bone marrow stem cell niche.
Estrogen-induced gene expression in bone marrow c-kit+ stem cells and stromal cells: identification of specific biological processes involved in the functional organization of the stem cell niche.
Sex, Age
View SamplesCanonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells.
An unexpected role for a Wnt-inhibitor: Dickkopf-1 triggers a novel cancer survival mechanism through modulation of aldehyde-dehydrogenase-1 activity.
Specimen part, Cell line
View SamplesSalt Stress response of salt-tolerant genotype FL478 compared to IR29
Comparing genomic expression patterns across plant species reveals highly diverged transcriptional dynamics in response to salt stress.
Specimen part
View SamplesSalt Stress response of salt-tolerant genotype Golden Promise compared to Maythorpe
Array-based genotyping and expression analysis of barley cv. Maythorpe and Golden Promise.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The demethylase JMJD2C localizes to H3K4me3-positive transcription start sites and is dispensable for embryonic development.
Specimen part, Cell line, Treatment
View SamplesEnzymes catalyzing the methylation of the 5-position of cytosine (mC) have essential roles in regulating gene expression, genome stability, and maintaining cellular identity. Recently Tet1, which is highly expressed in embryonic stem (ES) cells, was found to oxidize the methyl group of mC converting it to 5-hydroxymethyl cytosine (hmC)3. Here, we present the genome-wide mapping of Tet1 and hmC in mouse ES cells. We show that Tet1 binds throughout the genome with the majority of binding sites located at transcription start sites (TSSs) and within genes. Similar to Tet1 and mC, also hmC is found throughout the genome and in particular in gene bodies. However, in contrast to mC, hmC is enriched at TSSs. Tet1 and hmC are associated with genes critical for the control of development and differentiation, which become methylated during differentiation. Surprisingly our results also suggest that Tet1 has a role in transcriptional repression. We show that Tet1 binds to a significant proportion of target genes that are positive for the Polycomb repressive histone mark H3K27me3, and that downregulation of Tet1 also leads to increased expression of a group of Tet1 target genes. In agreement with a potential repressive function, we show that Tet1 associates with the Sin3A co-repressor complex, which also co-localises with Tet1 throughout the genome. We propose that Tet1 fulfils dual functions in transcriptional regulation, where it fine-tunes DNA methylation and associates with the Sin3A co-repressor complex to prevent transcriptional activation.
TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity.
Specimen part
View SamplesWe have mapped transcriptional changes after depletion of the histone demethylases JMJD2C/GASC1/KDM4C and JMJD2A/KDM4A alone or in combination in the esophageal squamous carcinoma cell line, KYSE150. The KYSE150 cell line contains an amplification of the JMJD2C locus.
The demethylase JMJD2C localizes to H3K4me3-positive transcription start sites and is dispensable for embryonic development.
No sample metadata fields
View SamplesDiffuse infiltrating gliomas are the most common primary brain malignancy found in adults, and Glioblastoma multiforme, the highest grade glioma, is associated with a median survival of 7 months. Transcriptional profiling has been applied to 85 gliomas from 74 patients to elucidate glioma biology, prognosticate survival, and define tumor sub-classes. These studies reveal that transcriptional profiling of gliomas is more accurate at predicting survival than traditional pathologic grading, and that gliomas characteristically express coordinately regulated genes of one of four molecular signatures: neurogenesis, synaptic transmission, mitotic, or extra-cellular matrix. Elucidation of these survival associated molecular signatures will aid in tumor prognostication and define targets for future directed therapy.
Gene expression profiling of gliomas strongly predicts survival.
Sex, Age, Specimen part, Disease stage
View Samples