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.
Transcriptome profiling of the theca interna in transition from small to large antral ovarian follicles.
Specimen part
View SamplesGranulosa 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.
Transcriptome profiling of granulosa cells from bovine ovarian follicles during atresia.
Specimen part
View SamplesThe 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).
Transcriptome analyses of ovarian stroma: tunica albuginea, interstitium and theca interna.
Specimen part
View SamplesOvarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells invaginate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 53) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 25 markers for GREL and other cells we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are separated from the stroma by a basal lamina. Around 130 days of gestation as the stroma expands laterally below the GREL cells on the surface thus establishing a sub-epithelial basal lamina and an epithelial-stromal interface, and it is at this stage that a mature surface epithelium develops from the GREL cells. The stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not invaginate into the ovary to form the granulosa cells of follicles.
A new model of development of the mammalian ovary and follicles.
Specimen part
View SamplesData defines for the first time a whole bladder transcriptome of UPEC cystitis in female C57BL/6 mice using genome-wide expression profiling to map early host response pathways stemming from UPEC colonization
Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection.
Sex, Age, Specimen part
View SamplesData defines for the first time a whole bladder transcriptome of UPEC cystitis in female CBA mice using genome-wide expression profiling to map early host response pathways stemming from UPEC colonization
Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of IL-10 for defense against bacterial urinary tract infection.
Sex, Age
View SamplesBackground: 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.
Function-based discovery of significant transcriptional temporal patterns in insulin stimulated muscle cells.
Specimen part, Cell line, Treatment
View SamplesThe 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.
The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila.
No sample metadata fields
View SamplesThe 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.
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
No sample metadata fields
View SamplesAlthough 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.
Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages.
No sample metadata fields
View Samples