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SRP178252
Mus musculus
2 Downloadable Samples
NextSeq 500
Description
R-spondin (Rspo) signaling is crucial for stem cell renewal and tissue homeostasis in the gastrointestinal tract. In the stomach, Rspo is secreted from myofibroblasts and controls epithelial gland regeneration by inducing proliferation of Wnt-responsive Axin2+ cells in the isthmus of the gland. Infection with H. pylori results in increased expression of stromal Rspo, leading to an expansion of Axin2+ isthmus stem cells and gland hyperplasia. Lgr5+ cells in the gland base are exposed to Rspo3 but the effects of this are not well understood. Here we demonstrate that apart from its activity as a mitogen, endogenous Rspo3 regulates gene expression of Lgr5+ cells in the gastric gland base. Surprisingly, Rspo3 induces differentiation within the Lgr5+ compartment towards secretory deep mucous cells. Moreover, the Rspo3-Lgr5 axis turns out to be a stimulus of epithelial antimicrobial defense. Infection with H. pylori induces a strong antimicrobial response, with Lgr5+ cells expressing antimicrobial compounds that are secreted into the lumen in an Rspo3-dependent manner. Depletion of Lgr5+ cells or knockout of Rspo3 in myofibroblasts leads to hyper-colonization of gastric glands, including the stem cell compartment, whereas systemic application of recombinant Rspo clears H. pylori from the glands. We provide an intriguing, unexpected feature of the Rspo3-Lgr5 axis in the stomach, exhibiting antimicrobial self-protection of the gland to protect the stem cell compartment from invading pathogens. Overall design: Lgr5eGFP reporter mice were infected with H. pylori for 2 months, uninfected mice served as controls. Mice were sacrificed and isolated, sorted Lgr5eGFP+ cells from the stomach antrum were used for single cell RNAseq using the 10x genome platform.
Publication Title
R-spondin-3 induces secretory, antimicrobial Lgr5<sup>+</sup> cells in the stomach.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 48 Downloadable Samples
- Illumina HiSeq 2000
Description
Differential gene expression as a consequence of PTCD1 loss Overall design: We used RNA from control and PTCD1 knockout mice to investigate changes at the RNA level in response to PTCD1 loss
Publication Title
PTCD1 Is Required for 16S rRNA Maturation Complex Stability and Mitochondrial Ribosome Assembly.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Insults to cellular health cause p53 protein accumulation and loss of p53 function leads to tumorigenesis. Thus, p53 has to be tightly controlled. Here we report that the BTB/POZ domain transcription factor PATZ1 (MAZR), previously known for its transcriptional suppressor functions in T lymphocytes, is a crucial regulator of p53. The novel inhibitory role of PATZ1 on the p53 protein marks it as a proto-oncogene. PATZ1 deficient cells have reduced proliferative capacity which we assess by RNASeq and real time cell growth rate analysis. PATZ1 modifies the expression of p53 target genes associated with cell proliferation gene ontology terms. Moreover, PATZ1 regulates several genes involved in cellular adhesion and morphogenesis. Significantly, treatment with the DNA damage inducing drug doxorubicin results in the loss of the PATZ1 transcription factor, as p53 accumulates. We find that PATZ1 binds to p53 and inhibits p53 dependent transcription activation. We examine the mechanism of this functional inhibitory interaction and demonstrate that PATZ1 excludes p53 from DNA binding. This study documents PATZ1 as a novel player in the p53 pathway. Overall design: RNA-seq was used to define differentially expressed genes in wild-type and PATZ1-/- MEFs. Each sample was represented in triplicate.
Publication Title
PATZ1 Is a DNA Damage-Responsive Transcription Factor That Inhibits p53 Function.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 51 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 36 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 15 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature aging. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with aging. Here we show that the FoxO transcription factor DAF-16 is activated in response to DNA damage during development while the DNA damage responsiveness of DAF-16 declines with aging. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA damage induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16 mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.
Publication Title
DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Sample Metadata Fields
Treatment
View Samples- Danio rerio
- 3 Downloadable Samples
- NextSeq 500
Description
Development of specialized cell types and structures in the vertebrate heart is regulated by spatially-restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development and function we used tomo-seq, combining high-throughput RNA sequencing with tissue sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development and function. Using our transcriptome map, we identified spatially restricted Wnt/ß-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/ß-catenin signaling at a specific developmental stage in the myocardium controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially-restricted molecular pathways critical for specific cardiac functions. Overall design: To generate spatially-resolved RNA-seq data for the developing zebrafish hearts (2 days post fertilization), we cryosectioned 3 hearts, extracted RNA from the individual sections, amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing. Sample Heart #1 is the primary sample. Heart #2 and #3 are biological replicates used for comparison.
Publication Title
Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Cardiomyopathies-associated metabolic pathologies (e.g. T2D and insulin resistance) are a leading cause of mortality. It is known that the association between the pathologies works in both directions, where heart failure can lead to metabolic derangements such as insulin resistance. This intricate crosstalk exemplifies the importance of a fine coordination between one of the most energy demanding organs and an equilibrated carbohydrate metabolism. In this light, to assist in the understanding of the role of insulin regulated glucose transporters and the development of cardiomyopathies, we set out to study GLUT12. GLUT12 is a novel insulin regulated GLUT expressed in the main insulin sensitive tissues such as cardiac and skeletal muscle and adipose tissue. This study investigates the role of GLUT12 in heart failure and diabetes by developing a model for glut12 deficiency in zebrafish. Overall design: 6 samples in total were analyzed. 3 replicates from control samples (injected with contol MO) and 3 replicates from glut12 morphant samples (injected with glut12 splice MO). In each sample 10 embryos were pooled.
Publication Title
GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all.
Publication Title
Transcriptional repressor Tbx3 is required for the hormone-sensing cell lineage in mammary epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
- NextSeq 500
Description
In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located at the wound border. Here, we show that tomo-seq can be used to identify whole-genome transcriptional profiles of the injury zone, the border zone and the healthy myocardium. Interestingly, the border zone is characterized by the re-expression of embryonic cardiac genes that are also activated after myocardial infarction in mouse and human, including targets of Bone Morphogenetic Protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts. Overall design: To generate spatially-resolved RNA-seq data for injured zebrafish hearts (3 and 7 days-post-injury), we cryosectioned samples, extracted RNA from the individual sections, and amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing.
Publication Title
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.
Sample Metadata Fields
Specimen part, Subject
View Samples