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accession-icon SRP057171
Sequential Notch activation regulates ventricular chamber development
  • organism-icon Mus musculus
  • sample-icon 82 Downloadable Samples
  • Technology Badge IconIlluminaHiSeq2500, IlluminaGenomeAnalyzerIIx

Description

Ventricular chambers are essential for the rhythmic contraction and relaxation that occurs in every hearbeat throughout life. Congenital abnormalities in ventricular chamber formation cause severe human heart defects. How the early trabecular meshwork of myocardial fibres forms and subsequently develops into mature chambers is still poorly understood. Here we show that Notch signalling first connects chamber endocardium and myocardium to sustain trabeculation and later coordinates ventricular patterning and compaction with coronary vessel development to give rise to the mature chamber via a temporal sequence of ligand signalling determined by the glycosyltransferase Manic Fringe (Mfng). The early endocardial expression of Mfng favours Dll4-Notch1 signalling, Which induces trabeculation in the developing ventricle.Ventricular maturation and compaction in turn require Mfng and Dll4 downregulation in the endocardium, Which allows myocardial Jag1- And Jag2- Signalling to Notch1 in this tissue.Timely and spatial perturbation of this signalling equilibrium severely disrupts heart chamber formation. Our results open a new research avenue into the pathogenesis of cardiomyopathies. Overall design: Dll4 and Notch1 conditional KOs using Nfact1 and/or Tie2 driven Cre expression: RNA was isolated from pooled whole hearts of 8 (Nfact1) or 9 (Tie2) E9.5 embryos per replicate. Dll4flox;Nfatc1-Cre and WT siblings (4 KO and 4 WT replicates), Notch1flox;Nfatc1-Cre and WT siblings (3 KO and 2 WT replicates), Dll4flox;Tie2-Cre and WT siblings (3 KO and 3 WT replicates). Jag1, Jag2 and Jag1Jag2 conditional KOs using cTnT driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. Jag1flox;cTnT-Cre and WT siblings (3 KO and 3 WT replicates), Jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). Jag1flox;jag2flox;cTnT-Cre and WT siblings (3 KO and 2 WT replicates). MFng Gain Of Function using Tie2 driven Cre expression: RNA was isolated from pooled heart ventricles of 4 E15.5 embryos per replicate. MFng;Tie2-Cre and WT siblings (4 GOF and 4 WT replicates). For Dll4, Noth1 and Jag1 KOs, libraries were prepared using the standard Illumina TrueSeq RNASeq library preparation kit and sequenced in a GAIIx Illumina sequencer using a 75bp single end elongation protocol. For Jag2 and Jag1Jag2 KOs and MFng GOF libraries were prepared prepared using the NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced in a HiSeq2500 Illumina sequencer using a 61bp single end elongation protocol

Publication Title

Sequential Notch activation regulates ventricular chamber development.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP060707
TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities.
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Dioxygenases of the TET family impact genome functions by converting 5-methylcytosine in DNA to 5-hydroxymethylcytosine, but the individual contribution of the three family members to differentiation and function of myeloid cells is still incompletely understood. Using cells with a deletion in the Tet2 gene, we show that TET2 contributes to the regulation of mast cell differentiation, proliferation and effector functions. The differentiation defect observed in absence of TET2 could be however completely rescued or further exacerbated by modulating TET3 activity, and it was primarily linked to dysregulated expression of the C/EBP family of transcription factors. In contrast, hyper-proliferation induced by the lack of TET2 could not be modified by TET3. Together, our data indicate the existence of both overlapping and unique roles of individual TET proteins in regulating myeloid cell gene expression, proliferation and function. Overall design: Total mRNA of FACS-sorted Kit+ FceRIa+ populations of primary bone marrow-derived mast cells (BMMCs) from Tet2-/- and Tet2+/+ animals was extracted and subjected to multiparallel sequencing.

Publication Title

TET2 Regulates Mast Cell Differentiation and Proliferation through Catalytic and Non-catalytic Activities.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP018707
Transcriptome along the murine developing gut
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Overall design: Transcriptional activity at the HoxD locus in the murine developing gut at E13, Differential gene expression analysis along the murine developing gut

Publication Title

Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP018708
Transcriptome in developing caeca
  • organism-icon Mus musculus
  • sample-icon 1 Downloadable Sample
  • Technology Badge IconIllumina Genome Analyzer II

Description

Hox genes are required for the development of the intestinal caecum, a major organ of species eating plants. We have analysed the transcriptional regulation of Hoxd genes in caecal buds and show that they are controlled by a series of enhancers located in a gene desert telomeric to the HoxD cluster. The start site of two neighboring and opposite long non-coding RNAs, Hotdog and Twin of Hotdog, specifically transcribed in the caecum, contacts the expressed Hoxd genes in the framework of a topological domain, a large domain of interactions, which ensures a robust transcription of these genes during caecum budding. We show that hedgehogs have kept this regulatory potential despite the absence of caecum, suggesting that these enhancers are used in other developmental situations. In this context, we discuss some striking similarities between the caecum and the limb buds, suggesting the implementation of a common budding tool-kit. Transcriptional activity at the HoxD locus in developing caeca at E13.5 Overall design: Transcriptional activity at the HoxD locus in developing caeca at E13.5

Publication Title

Multiple enhancers regulate Hoxd genes and the Hotdog LncRNA during cecum budding.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP065571
Sequential ligand-dependent Notch signaling activation regulates valve primordium formation and morphogenesis
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

Our studies identify a mechanism of signaling crosstalk during valve morphogenesis that sheds light on the origin of congenital heart defects associated with reduced Notch function. Overall design: Aortic and pulmonary cardiac valves were isolated by laser microdissection from WT and Jag1flox;Nkx2.5-Cre mouse embryos at stage E14.5, and their expression profile characterized by RNA-Seq.

Publication Title

Sequential Ligand-Dependent Notch Signaling Activation Regulates Valve Primordium Formation and Morphogenesis.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE25414
Expression data from human blood samples
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Genetic factors contribute to the development of ischemic stroke but their identity remains largely unknown. We tested the association with ischemic stroke of 210 single nucleotide polymorphisms (SNPs) associated with pathways functionally related to stroke. We observed an association between the rs7956957 SNP in LRP1 and next performed microarrays analysis in healthy individuals to investigate possible associations of LRP genotypes with the expression of other genes.

Publication Title

Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE24265
Expression data from human brain samples
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH.

Publication Title

Brain perihematoma genomic profile following spontaneous human intracerebral hemorrhage.

Sample Metadata Fields

Sex, Age, Specimen part

View Samples
accession-icon SRP097979
Next Generation Sequencing of Gene expression changes in U2OS osteosarcoma cells with PML silencing
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge IconIllumina HiScanSQ

Description

We used next generation sequencing to analyze the gene expression changes in U2OS osteosarcoma cells expressing shRNA targeting the promyelocytic leukemia (PML) gene transcripts Overall design: cDNA libraries of U2OS cells expressing control shRNA or shRNA targeting PML were generated from one biological replicate

Publication Title

PML nuclear bodies contribute to the basal expression of the mTOR inhibitor DDIT4.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP192834
Transcriptomic of MKD (MUC1 kidney disease) patient compares to normal derived kidney epithelial cells
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

bulk RNAseq of MUC1 kidney disease patient derived kidney epithelial cells compare to normal kidney cells. The goal of this study was to elucidate the biological mechanism underlying MUC1 kidney disease using MUC1 expressing cells derived from either a patient or a healthy individual kidney Overall design: Bulk RNAseq of immortalized patient compare to normal cell line

Publication Title

Small Molecule Targets TMED9 and Promotes Lysosomal Degradation to Reverse Proteinopathy.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE9747
Regulation of gene expression in MDAMB231 breast cancer cells by Parvin-beta in 2D vs 3D culture conditions
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Parvin-beta is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-beta contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-beta expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-beta was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Gene expression profiles of vector control and Parvin-beta transfected MDA-MB-231 cells cultured on (A) monomeric type I collagen coated plastic, (B) embedded in a type I collagen gel, and (C) embedded in basement membrane (growth factor reduced Matrigel), were compared. Interestingly, Parvin-beta re-expression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPARgamma) and a concomitant increase in lipogenic gene expression as a downstream effector of PPARgamma. Importantly, Parvin-beta suppressed breast cancer growth in vivo with associated decreased proliferation. These data suggest that Parvin-beta might influence breast cancer progression..

Publication Title

Parvin-beta inhibits breast cancer tumorigenicity and promotes CDK9-mediated peroxisome proliferator-activated receptor gamma 1 phosphorylation.

Sample Metadata Fields

No sample metadata fields

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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