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GSE27630
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The choroid plexuses (ChPs) are the main regulators of cerebrospinal fluid (CSF) composition and thereby also control the composition of a principal source of signaling molecules that is in direct contact with neural stem cells in the developing brain. The regulators of ChP development mediating the acquisition of a fate that differs from the neighboring neuroepithelial cells are poorly understood. Here, we demonstrate in mice a crucial role for the transcription factor Otx2 in the development and maintenance of ChP cells. Deletion of Otx2 by the Otx2-CreERT2 driver line at E9 resulted in a lack of all ChPs, whereas deletion by the Gdf7-Cre driver line affected predominately the hindbrain ChP, which was reduced in size, primarily owing to an increase in apoptosis upon Otx2 deletion. Strikingly, Otx2 was still required for the maintenance of hindbrain ChP cells at later stages when Otx2 deletion was induced at E15, demonstrating a central role of Otx2 in ChP development and maintenance. Moreover, the predominant defects in the hindbrain ChP mediated by Gdf7-Cre deletion of Otx2 revealed its key role in regulating early CSF composition, which was altered in protein content, including the levels of Wnt4 and the Wnt modulator Tgm2. Accordingly, proliferation and Wnt signaling levels were increased in the distant cerebral cortex, suggesting a role of the hindbrain ChP in regulating CSF composition, including key signaling molecules. Thus, Otx2 acts as a master regulator of ChP development, thereby influencing one of the principal sources of signaling in the developing brain, the CSF.
Publication Title
The transcription factor Otx2 regulates choroid plexus development and function.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 10 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Naïve and primed pluripotency is characterized by distinct signaling requirements, transcriptomes and developmental properties, but both cellular states share key transcriptional regulators, Oct4, Sox2 and Nanog. Here we demonstrate that transition between these two pluripotent states is associated with widespread Oct4 relocalization, mirrored by global rearrangement of enhancer chromatin landscapes. Our genomic and biochemical analyses identified candidate mediators of primed state-specific Oct4 binding, including Otx2 and Zic2/3. Even in the absence of other differentiation cues, premature Otx2 overexpression is sufficient to exit the naïve state, induce transcription of a large subset of primed pluripotency-associated genes and redirect Oct4 to thousands of previously inaccessible sites. However, ability of Otx2 to engage new enhancer regions is determined by its levels, cis-encoded properties of the sites and signaling environment. Our results illuminate regulatory mechanisms underlying pluripotency and suggest that capacity of transcription factors such as Otx2 and Oct4 to function as pioneers is highly context-dependent Overall design: transcription profile of ESCs and EpiLCs to analzye changes during differentiation and the effect of Otx2 loss and overexpression on the differentiation properties
Publication Title
Reorganization of enhancer patterns in transition from naive to primed pluripotency.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
L1 retrotransposons are active elements in the genome, capable of mobilization in neuronal progenitor cells. Previously, we showed that chromatin remodeling during neuronal differentiation allows for a transient stimulation of L1 transcription. The activity of L1 retrotransposons during brain development can impact gene expression and neuronal function. Here we show that L1 neuronal retrotransposition in rodents is increased in the absence of MeCP2, a protein involved in global methylation and human neurodevelopmental diseases. Using neuronal progenitor cells derived from human induced pluripotent stem cells and human tissues, we revealed that Rett syndrome patients, with MeCP2 mutations, have increased susceptibility for L1 retrotransposition. Our data demonstrate that disease-related genetic mutations can influence the frequency of neuronal L1 retrotransposition, thereby increasing brain-specific genetic mosaicism.
Publication Title
A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Adult hematopoietic stem cells (HSCs) reside primarily in bone marrow. However, hematopoietic stresses such as myelofibrosis, anemia, pregnancy, infection or myeloablation can mobilize HSCs to the spleen and induce extramedullary hematopoiesis (EMH). While the bone marrow HSC niche has been studied intensively, the EMH niche has received little attention. Here, we systematically assessed the physiological sources of the key niche factors, SCF and CXCL12, in the mouse spleen after EMH induction by cyclophosphamide plus granulocyte colony-stimulating factor, blood loss, or pregnancy. In each case, Scf was expressed by endothelial cells and Tcf21+ stromal cells, primarily around sinusoids in red pulp, while Cxcl12 was expressed by a subset of Tcf21+ stromal cells. EMH induction markedly expanded the Scf-expressing endothelial cells and stromal cells by inducing proliferation. Most splenic HSCs were adjacent to Tcf21+ stromal cells in red pulp. Conditional deletion of Scf from spleen endothelial cells or Scf or Cxcl12 from Tcf21+ stromal cells severely reduced spleen EMH and reduced blood cell counts without affecting bone marrow hematopoiesis. Endothelial cells and Tcf21+ stromal cells thus create the splenic EMH niche, which is necessary for the physiological response to diverse hematopoietic stresses.
Publication Title
A perisinusoidal niche for extramedullary haematopoiesis in the spleen.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the mRNA profile of aged mice (24 months old) fed either a control diet or a diet containing Rapamycin (14 ppm) for 3 months. After drug treatement, the hearts of the mice were removed and total mRNA was removed from the tissue. Analysis revealed that there were 700 significantly differentially expressed genes between the control fed group and the Rapamycin diet group by our analysis. Overall design: Heart tissue samples from age-matched control mice (n=10) and rapamycin fed mice (n=10) were extracted for total RNA. The samples were sequenced using Illumina HiSeq 2000 (50 basepair paired-end sequencing). The sequencing yielded quality scores greater than 30 with an average of 10 million reads per sample. 34,293 genes were mapped back to the MGSCv37 C57BL/6J mouse genome (maximum paired distance=300 and minimum=130, minimum number of reads per mapping = 5, maximum number of mismatches= 2, with the reads being mapped to unique sites in the genome).
Publication Title
Late-life rapamycin treatment reverses age-related heart dysfunction.
Sample Metadata Fields
Age, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
iPSC were obtained from DPC from TRPC6-mut patient, a idiopathic autistic patient and a control. Original DPC and iPSC obtained were submited to expression analysis in order to check if the expression pattern obtained for the iPSC cells were closer related to embyonic cells than to the original DPC
Publication Title
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
As TRPC6 channel induces CREB-mediated trancription, Dental pulp cells from TRPC6-mut patient and from 6 controls were analyzed in order to verify if the disruption of TRPC6 leads to transcriptional changes.
Publication Title
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons.
Sample Metadata Fields
Specimen part
View Samples