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GSE49505
Bos taurus
19 Downloadable Samples
Affymetrix Bovine Genome Array (bovine)
Description
Thecal tissue forms a layer around the follicle just prior to antral stage and grows with the follicle (containing an oocyte) as it matures. The innermost component (theca interna) supplies hormones and other factors necessary to the growth and development of the granulosa and oocyte. Most follicles regress and die (become atretic) at the antral stage, and this process as well as development of the follicle are undoubtedly influenced by the theca.
Publication Title
Transcriptome profiling of the theca interna in transition from small to large antral ovarian follicles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that -catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of -catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.
Publication Title
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Although the role of macrophage colony stimulating factor (M-CSF/CSF-1) in homeostasis and disease processes has been studied extensively in mice, little is known of the impact of this cytokine on differentiated human macrophages. Here we show that, in contrast to its effects on mouse bone marrow-derived macrophages (BMM), CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Using expression profiling, we show that CSF-1 dynamically regulated the expression of several genes that encode chemokines and chemokine receptors (e.g. CXCL10/IP-10, CXCL2, CCL7, SDF2L1, CXCR4) in HMDM. CSF-1 also upregulated the expression of several genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7 and DHCR24), while expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Although the CSF-1/CSF-1R system has been proposed as a target for the treatment of inflammatory and metastatic disease based on studies in rodents, this is the first systematic analysis of the effects of CSF-1 on mature human macrophages. Our data demonstrates that CSF-1 represents a further link between inflammation and cardiovascular disease, inflammtion and immunity.
Publication Title
Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Granulosa cells mature and die as ovarian follicles enlarge and die (undergo atresia) under the influence of hormones and intrafollicular factors. Later in follicular development, a fluid-filled antrum is formed, a process which is accompanied by a high rate of atresia. These small antral follicles (5 mm or less in diameter in the cow) contain granulosa of 2 different phenotypes, rounded or columnar, whereas follicles larger than 5 mm have the rounded phenotype only. Prior to ovulation, in larger follicles greater than 10 mm in size, the granulosa begin to migrate and differentiate in preparation for oocyte release and formation of the corpus luteum.
Publication Title
Transcriptome profiling of granulosa cells from bovine ovarian follicles during atresia.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 18 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
The ovary has specialized stromal compartments, including the tunica albuginea, interstitial stroma and theca interna, which develops concurrently with the follicular antrum. To characterize the molecular determinants of these compartments, stroma adjacent to preantral follicles (pre-theca), interstitium and tunica albuginea were laser microdissected (n = 4 per group) and theca interna was dissected from bovine antral follicles (n = 6).
Publication Title
Transcriptome analyses of ovarian stroma: tunica albuginea, interstitium and theca interna.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
Signalling via the colony stimulating factor 1 receptor (CSF1R) controls the survival, differentiation and proliferation of macrophages which are a source of the somatic growth factor insulin growth factor 1 (IGF1). Treatment of newborn mice with CSF1 has previously been shown to produce an increase in somatic growth rate and we hypothesised that treatment of neonatal low birth weight (LBW) rats with CSF1 would do the same. Growth rates were not affected, yet CSF1 treatment caused an unexpectedly large, but reversible increase in liver size and hepatic fat deposition in both normal and LBW rats. By transcriptional profiling, we have highlighted numerous CSF1-regulated genes known to be involved in lipid droplet formation in the liver and novel candidate genes for further investigation. In contrast to mice and weaner pigs, CSF1 treatment did not increase hepatocyte proliferation in neonatal rats, rather the data were consistent with increased macrophage proliferation instead. This suggests that Kupffer cells promote lipid accumulation in neonates and treatment to ablate CSF1R signalling may reverse lipid accumulation in the liver.
Publication Title
Macrophage colony-stimulating factor increases hepatic macrophage content, liver growth, and lipid accumulation in neonatal rats.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 53 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Background: Insulin's effect on protein synthesis (translation of transcripts) and post-translational modifications, especially those involving reversible modifications such as phosphorylation of various signaling proteins, are extensively studied. On the other hand, insulin's effect on the transcription of genes, especially of transcriptional temporal patterns, is not well investigated in the literature.
Publication Title
Function-based discovery of significant transcriptional temporal patterns in insulin stimulated muscle cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 194 Downloadable Samples
NextSeq 500
Description
We introduce a microfluidic platform that enables off-chip single-cell RNA-seq after multigenerationa lineage tracking under controlled culture conditions. Overall design: Examination of lineage and cell cycle dependent transcriptional profiles in two cell types
Publication Title
A microfluidic platform enabling single-cell RNA-seq of multigenerational lineages.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- NextSeq 500
Description
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of T regulatory (Treg) cells and make autoantibodies, but seldom develop autoimmunity. We show that similarly, Dock8-/- mice have decreased numbers and impaired in vitrofunction of Treg cells, but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Treg cells develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite normal percentage and in vitro function of Treg cells, suggesting that deficient T effector cell function might protect DOCK8 deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2 driven STAT5 phosphorylation in Treg cells. DOCK8 localizes within the lamellar actin ring of the Treg cell immune synapse (IS). Dock8-/- Treg cells have abnormal TCR-driven actin dynamics, decreased adhesiveness, altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the co-stimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Treg cells. Overall design: CD4+CD25+CD39+YFP+ and CD4+CD25+CD39+YFP- Treg cells were isolated from the spleen and lymph nodes of Foxp3YFP-Cre/+/Dock8flox/flox mice. Treg cells were then cultured overnight in complete media alone or in the presence of media + anti-CD3+CD28 beads (1 bead per cell). After 16 hours, cells were harvested and the RNA was isolated. For unstimulated samples, there were 4 independent YFP- samples and 6 independent YFP+ samples. For bead stimulated samples, there were 3 independent YFP- samples and 2 YFP+ samples.
Publication Title
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate NF-kB family members. We have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways, and triggered activation of a STAT binding activity. Genetic experiments showed that the JAK kinase Hopscotch was involved in the control of the viral load in infected flies, and was required, though not sufficient, for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third evolutionary conserved innate immunity pathway operates in drosophila and counters viral infection.
Publication Title
The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila.
Sample Metadata Fields
No sample metadata fields
View Samples