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SRP063013
Mus musculus
12 Downloadable Samples
Illumina HiSeq 2500
Description
Pancreatic islet endocrine cell and endothelial cell (EC) interactions mediated by vascular endothelial growth factor-A (VEGF-A) signaling are important for islet endocrine cell differentiation and the formation of highly vascularized islets. To dissect how VEGF-A signaling modulates intra-islet vasculature and innervation, islet microenvironment, and ß cell mass, we transiently increased VEGF-A production by ß cells. VEGF-A induction dramatically increased the number of intra-islet ECs but led to ß cell loss. After withdrawal of the VEGF-A stimulus, ß cell mass, function, and islet structure normalized as a result of a robust, but transient, burst in proliferation of pre-existing ß cells. Bone marrow-derived macrophages (MFs) recruited to the site of ß cell injury were crucial for the ß cell proliferation, which was independent of pancreatic location and circulating factors such as glucose. Identification of the signals responsible for the proliferation of adult, terminally differentiated ß cells will improve strategies aimed at ß cell regeneration and expansion. Overall design: Examination of RNA profiles from isolated whole islets from RIP-rtTA; TetO-VEGF-A mice with no doxycycline (Dox) treatment (3 samples) and after 1 week of Dox (3 sample); and islet-derived macrophages (3 samples) and endothelial cells (3 samples) isolated from dispersed purified islets from RIP-rtTA; TetO-VEGF-A mice after 1 week Dox treatment by fluorescence-activated cell sorting using antibodies against CD11b and CD31, respectively.
Publication Title
Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The generation of properly functioning gametes in vitro, a key goal in developmental/reproductive biology, requires multi-step reconstitutions of complex germ cell development. Based on the logic of primordial germ cell (PGC)-specification, we demonstrate here the generation of PGC-like cells (PGCLCs) in mice with robust capacity for spermatogenesis from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) through epiblast-like cells (EpiLCs), a cellular state highly similar to pre-gastrulating epiblasts, but distinct from epiblast stem cells (EpiSCs). The global transcription profiles, epigenetic reprogramming, and cellular dynamics during PGCLC induction from EpiLCs are a meticulous capture of those associated with PGC specification from the epiblasts. Furthermore, we identify Integrin-beta 3 and SSEA1 as markers that purify PGCLCs with spermatogenic capacity free from tumorigenic undifferentiated cells. With the reconstitution of PGC specification pathway from the naive inner cell mass state, our study defines a paradigm for the essential step of in vitro gametogenesis.
Publication Title
Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Congenital heart defects (CHDs) occur in 0.51% of live births, yet the underlying genetic etiology remains mostly unknown. Recently, a new source of myocardial cells, namely the second heart field (SHF), was discovered in the splanchnic mesoderm. Abnormal development of the SHF leads to a spectrum of outflow tract defects, such as persistent truncus arteriosus and tetralogy of Fallot. Intracellular Ca2+ signaling is known to be essential formany aspects of heart biology including heart development, but its role in the SHF is uncertain. Here, we analyzed mice deficient for genes encoding inositol 1,4,5-trisphosphate receptors (IP3Rs), which are intracellular Ca2+ release channels on the endo/sarcoplasmic reticulum that mediate Ca2+ mobilization. Mouse embryos that are double mutant for IP3R type 1 and type 3 (IP3R1/IP3R3/) show hypoplasia of the outflow tract and the right ventricle, reduced expression of specific molecular markers and enhanced apoptosis ofmesodermal cells in the SHF. Gene expression analyses suggest that IP3R-mediated Ca2+ signalingmay involve, at least in part, theMef2CSmyd1 pathway, a transcriptional cascade essential for the SHF. These data reveal that IP3R type 1 and type 3 may play a redundant role in the development of the SHF.
Publication Title
Inositol 1,4,5-trisphosphate receptors are essential for the development of the second heart field.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The germ cell lineage ensures reproduction and heredity in metazoans. Primordial germ cells (PGCs) in mice are induced in pluripotent epiblast cells by BMP4 and WNT3, yet their mechanism of action remains elusive. Here, using in vitro PGC specification system, we show that WNT3, but not BMP4, induces many transcription factors associated with mesoderm in epiblast-like cells (EpiLCs) through beta-CATENIN. Among these, T (BRACHYURY), a classical and conserved mesodermal factor, was essential for robust activation of Blimp1 and Prdm14, two of the germline determinants. T, but not SMAD1 or beta-CATENIN/TCF1, binds distinct regulatory elements of both Blimp1 and Prdm14, and directly up-regulates these genes without BMP4 and WNT3. Without BMP4, a program induced by WNT3 prevents T from activating Blimp1 and Prdm14, demonstrating that BMP4 is permissive for PGC specification. These findings establish a fundamental role of a mesodermal gene in PGC specification, a potentially evolutionarily conserved mechanism across metazoans.
Publication Title
A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Bovine leukemia virus (BLV) Tax is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.
Publication Title
Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Human T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study, a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis.
Publication Title
Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
There is an increasing interest on the role of Alternative splicing (AS) in different pathologies. The Affymetrix Human Transcriptome Array (HTA 2.0) can be used to explore AS very efficiently. However, the interpretation software provided by its vendor (TAC 3.0) does not fully exploit its potential and can only be applied to case-control studies. EventPointer is an R package to identify Alternative Splicing events using HTA 2.0 arrays. It can be applied to complex experimental designs. The software provides a list of the detected events indicating the type of event (cassette, alternative 3, etc.), their statistical significance, and affected protein domains affected. The false positive rate is very low (the first detected false positive was ranked in the 149th position). EventPointer is publicly available at GitHub.
Publication Title
EventPointer: an effective identification of alternative splicing events using junction arrays.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression from Wild-type and NFAT5 knock-out Mouse Embryonic Fibroblasts
Publication Title
Transcriptional regulation of gene expression during osmotic stress responses by the mammalian target of rapamycin.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression from WT and NFAT5 KO primary macrophage cultures.
Publication Title
Gene expression induced by Toll-like receptors in macrophages requires the transcription factor NFAT5.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Muscle biopsies from biceps and deltoid were taken from 5 patients with FSHD, 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips.
Publication Title
Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples