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GSE69408
Homo sapiens
39 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Aging within the human hematopoietic system associates with increased incidence of anemia and myeloid neoplasms, decreased bone marrow (BM) cellularity and reduced adaptive immune responses. Similar phenotypes have been observed in mice and shown, at least in part, to involve hematopoietic stem cells (HSCs). However, evidence supporting such an association within human hematopoiesis is still sparse and prompted us to detail characteristics of human hematopoietic stem and progenitor cells throughout ontogeny.
Publication Title
Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias.
Sample Metadata Fields
Specimen part
View Samples- Anopheles gambiae
- 104 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
Anopheles gambiae,the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis ofA. gambiaehead and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.
Publication Title
Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The ability of oncogenes to provoke cancer is harnessed by regulators that control cell proliferation or induce apoptosis, and bypass of these checkpoints is a hallmark of malignancies. Myc oncoproteins are overexpressed in ~70% of all cancers and induce numerous transcription targets that regulate cell growth, metabolism, and the ribosome machinery. We used the E-Myc mouse model from which one can directly compare expression profiles of wild type versus Myc-expressing B220+ pre-malignant lymphocytes and also queried differences in gene expression that ensue following the neoplastic switch to lymphoma (Nilsson et al., 2005 - PMID:15894264 and Keller et al. 2010 - PMID:20598117).
Publication Title
Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Different fibroblast cells (eight in total) with different inhibitory capacity were analyzed and compared for their gene expression profile by whole genome microarray.
Publication Title
Confrontation of fibroblasts with cancer cells in vitro: gene network analysis of transcriptome changes and differential capacity to inhibit tumor growth.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NF1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing FoxF1.
Publication Title
Forkhead Box F1 promotes breast cancer cell migration by upregulating lysyl oxidase and suppressing Smad2/3 signaling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 27 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Primordial follicle assembly is the process by which ovarian primordial follicles are formed. During follicle assembly oocyte nests break down and a layer of pre-granulosa cells surrounds individual oocytes to form primordial follicles. The pool of primordial follicles formed is the source of oocytes for ovulation during a females reproductive life. Complex networks of cellular signaling and gene expression are essential for any biological process. A systems biology experimental approach provides a global view of these gene relationships in a particular developmental process. The current study utilized a systems approach to detect all genes that are differentially expressed in response to seven different growth factor and hormone treatments known to influence primordial follicle assembly in a neonatal rat ovary culture system. One novel growth factor, basic fibroblast growth factor (FGF2), was experimentally determined to inhibit follicle assembly. The different growth factor and hormone treatments were all found to affect the same physiological pathways, but each treatment affected a unique set of differentially expressed genes (signature gene set). A gene bionetwork analysis identified gene modules of coordinately expressed interconnected genes and it was found that different gene modules appear to accomplish distinct tasks during primordial follicle assembly. Unique gene networks were identified for a number of the modules and signature gene sets. Predictions of physiological pathways important to follicle assembly were validated using ovary culture experiments in which ERK1/2 (MAPK1) activity was increased. A number of the highly interconnected genes in these gene networks have previously been linked to primary ovarian insufficiency (POI) and polycystic ovarian disease syndrome (PCOS). Observations have identified novel factors and gene networks that regulate primordial follicle assembly. This systems approach has helped elucidate the molecular control of primordial follicle assembly and provided potential therapeutic targets for the treatment of ovarian disease.
Publication Title
Gene bionetworks that regulate ovarian primordial follicle assembly.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Neurotrophins are growth factors that are known to have a role in promoting cell survival and differentiation. The focus of the current study is to examine the role of neurotrophins in regulating ovarian primordial follicle development. Ovaries from 4-day old rats were placed into organ culture and cultured for 10 days in the absence or presence of neurotrophin-3 (NT3), brain-derived neurotrophic factor (BDNF), or nerve growth factor (NGF). Treatment of ovaries with NT3 resulted in a significant (P<0.01) increase in primordial follicle development (i.e. primordial to primary follicle transition). Treatment with BDNF at high doses of 100250 ng/ml also significantly (P<0.01) increased primordial follicle development, but NGF had no effect. Immunohistochemical studies determined that NT3 was present in granulosa cells, interstitial tissue, and in the oocytes of primordial and primary follicles. The NT3 receptor NTRK3 was present in oocytes at all stages of development. Analysis of ovaries that contain predominantly primordial follicles demonstrated the transcripts for NT3, NTRK3, NGF, and the BDNF/neurotrophin-4 (NT4) receptor NTRK2 are expressed, while BDNF, NT4, and the NGF receptor NTRK1 are not detectable. Inhibition of the NTRK3 receptor with the tyrophostin AG 879 resulted in oocyte death and a significant (P<0.01) reduction in follicle pool size. Inhibition of the NTRK receptors with K252a slowed primordial to primary follicle transition. A microarray analysis demonstrated that a small number of genes were differentially expressed after NT3 treatment. Observations indicate that the neurotrophin NT3, acting through the NTRK3 receptor in oocytes, promotes the primordial to primary follicle transition. Reproduction (2009) 138, pp. 697-707
Publication Title
Neurotrophin NT3 promotes ovarian primordial to primary follicle transition.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Primordial follicle assembly is a process that occurs in the embryonic or early post natal ovary in which oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGFbeta-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system for two days to measure the effect of these factors on follicle assembly. In addition, ovaries were cultured and treated for ten days to determine the potential of CTGF and TGFbeta-1 to manipulate the primordial follicle pool size over a longer developmental time period. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. TGFbeta-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGFbeta-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGFbeta-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGFbeta-1 stimulates primordial follicle assembly and TGFbeta-1 can decrease the primordial follicle pool size. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. CTGF is one of the first growth factors shown to promote primordial follicle assembly, while TGFbeta-1 is one of the first factors shown to decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan.
Publication Title
Induction of ovarian primordial follicle assembly by connective tissue growth factor CTGF.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The oocytes found within the primordial follicles of mammalian ovaries remain quiescent for months to years until they receive the appropriate signals to undergo the primordial to primary follicle transition and initiate folliculogenesis. The molecular mechanisms and extracellular signaling factors that regulate this process remain to be fully elucidated. The current study investigates the mechanisms utilized by anti-Mllerian hormone (AMH; i.e. Mllerian inhibitory substance) to inhibit the primordial to primary follicle transition. Ovaries from 4-day-old rats were placed into organ culture and incubated in the absence or presence of AMH, either alone or in combination with known stimulators of follicle transition, including basic fibroblast growth factor (bFGF), kit ligand (KITL), or keratinocyte growth factor (KGF). Following 10 days of culture, the ovaries were sectioned, stained, and morphologically evaluated to determine the percentage of primordial versus developing follicles. As previously demonstrated, AMH treatment decreased primordial to primary follicle transition. Interestingly, AMH inhibited the stimulatory actions of KITL, bFGF, and KGF. Therefore, AMH can inhibit the basal and stimulated development of primordial follicles. To investigate the mechanism of AMH actions, the influence AMH has on the ovarian transcriptome was analyzed. AMH treatment when compared with controls was found to alter the expression of 707 genes. The overall effect of AMH exposure is to decrease the expression of stimulatory factors, increase the expression of inhibitory factors, and regulate cellular pathways (e.g. transforming growth factor beta signaling pathway) that result in the inhibition of primordial follicle development. Analysis of the regulatory factors and cellular pathways altered by AMH provides a better understanding of the molecular control of primordial follicle development.
Publication Title
Actions of anti-Mullerian hormone on the ovarian transcriptome to inhibit primordial to primary follicle transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells.
Publication Title
Glial-derived neurotrophic factor promotes ovarian primordial follicle development and cell-cell interactions during folliculogenesis.
Sample Metadata Fields
No sample metadata fields
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