Gene expression profile of MRKHS patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE52609 | GEO | 2013/11/22
SECONDARY ACCESSION(S): PRJNA229474
REPOSITORIES: GEO
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Project description:The gene expression profile of vaginal cells isolated from MRKHS patients, compared with those without MRKHS, presented alterations of developmental genes such as HOXB family, the Notch ligands JAG1 and DLL1 and MUC1, which can represent key elements in the pathogenesis of MRKHS, thus suggesting a potential alteration of networks involved in the formation of the female reproductive tract. This study included sixteen MRKHS patients, diagnosed by clinical examination, trans abdominal and pelvic ultrasonography, nuclear magnetic resonance (NMR) and/or vaginoscopy, that underwent reconstruction of neovagina in the Department of Gynecologic-Obstetrical and Urologic Sciences of Sapienza University of Rome between 2007 and 2011, and five control subjects with no known reproductive tract defects or developmental malformations. 8 patients and 5 controls were analyzed using Illumina beadarray.
2013-11-22 | E-GEOD-52609 | biostudies-arrayexpress
Project description:Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival by interacting with Notch ligands on adjacent cells. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remain unclear. In this report we demonstrate that the Notch ligand Dll1 on CD4+ T cells transduces signals required for the maintenance of activated CD4+ T cells without affecting Notch signaling in the same cells. T cell-specific Dll1-deficient (Dll1-/-) mice did not show any defect in T cell development in thymus or spleen. Co-transfer of CD4+ T cells from Dll1-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1-/- mice compared with control cells. Dll1-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data highlight Dll1 as an independent regulator of Notch-signaling for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses The mRNA expression in activated CD4+ T cells from mouse was obtained by DNA microarray analysis. These mRNA expression was compared.
2016-01-09 | E-GEOD-76693 | biostudies-arrayexpress
Project description:Notch expressed on CD4+ T cells transduces signals that mediate their effector functions and survival by interacting with Notch ligands on adjacent cells. Although Notch signaling is known to be cis-inhibited by Notch ligands expressed on the same cells, the role of Notch ligands on T cells remain unclear. In this report we demonstrate that the Notch ligand Dll1 on CD4+ T cells transduces signals required for the maintenance of activated CD4+ T cells without affecting Notch signaling in the same cells. T cell-specific Dll1-deficient (Dll1-/-) mice did not show any defect in T cell development in thymus or spleen. Co-transfer of CD4+ T cells from Dll1-/- and control mice into recipient mice followed by immunization revealed a rapid decline of CD4+ T cells from Dll1-/- mice compared with control cells. Dll1-/- mice exhibited lower clinical scores of experimental autoimmune encephalitis than control mice. The expression of Notch target genes in CD4+ T cells from Dll1-/- mice was not affected, suggesting that Dll1 deficiency in T cells does not affect cis Notch signaling. Overexpression of the intracellular domain of Dll1 in Dll1-deficient CD4+ T cells partially rescued impaired survival. Our data highlight Dll1 as an independent regulator of Notch-signaling for the survival of activated CD4+ T cells, and provide new insight into the physiological roles of Notch ligands as well as a regulatory mechanism important for maintaining adaptive immune responses
2016-01-09 | GSE76693 | GEO
Project description:BACKGROUND: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. CONCLUSIONS/SIGNIFICANCE: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes. Four organs (liver, spleen, thymus, brain) of the Dll1 mutant mouse line analysed by cDNA microarray technology. Experiments include four biological replicates for reference (wildtype) and mutant animals. Two technical replicates for each mutant mouse were performed. As reference pooled RNA of the same organ was used. 50% of the chip hybridisations are dye sway experiments.
2009-03-01 | E-GEOD-12954 | biostudies-arrayexpress
Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.
2014-01-29 | E-GEOD-49892 | biostudies-arrayexpress
Project description:BACKGROUND: The Notch signaling pathway is an evolutionary conserved signal transduction pathway involved in embryonic patterning and regulation of cell fates during development and self-renewal. Recent studies have demonstrated that this pathway is integral to a complex system of interactions, involving as well other signal transduction pathways, and implicated in distinct human diseases. Delta-like 1 (Dll1) is one of the known ligands of the Notch receptors. The role of the Notch ligands is less well understood. Loss-of-function of Dll1 leads to embryonic lethality, but reduction of Delta-like 1 protein levels has not been studied in adult stage. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the haploinsufficient phenotype of Dll1 and a missense mutant Dll1 allele (Dll1(C413Y)). Haploinsufficiency leads to a complex phenotype with several biological processes altered. These alterations reveal the importance of Dll1 mainly in metabolism, energy balance and in immunology. The animals are smaller, lighter, with altered fat to lean ratio and have increased blood pressure and a slight bradycardia. The animals have reduced cholesterol and triglyceride levels in blood. At the immunological level a subtle phenotype is observed due to the effect and fine-tuning of the signaling network at the different levels of differentiation, proliferation and function of lymphocytes. Moreover, the importance of the proteolytic regulation of the Notch signaling network emphasized. CONCLUSIONS/SIGNIFICANCE: In conclusion, slight alterations in one player of Notch signaling alter the entire organism, emphasizing the fine-tuning character of this pathway in a high number of processes.
2009-03-01 | GSE12954 | GEO
Project description:The Notch signaling pathway is a cell-cell communication system with fundamental roles in embryonic development and the nervous system, including neural stem cell proliferation and differentiation. To investigate the multivalency effect of ligands on the activation of the Notch receptor, we treated iPSc-derived neuroepithelial stem-like (lt-NES) cells with different Jag1 nanopatterns on DNA origami nanostructures.
2023-11-23 | E-MTAB-12439 | biostudies-arrayexpress
Project description:Salivary adenoid cystic carcinoma (ACC) is a rare but biologically unique biphasic tumor, consisting of malignant myoepithelial and luminal epithelial cells. MYB and Notch signaling have been implicated in the pathophysiology of these tumors, but in vivo descriptions of these two programs in human tumors and investigation into their active coordination remain incomplete. We utilized single cell RNA-sequencing to profile human head and neck ACC, including the first comparison of primary ACC with a matched local recurrence. We define expression heterogeneity in these rare tumors, uncovering previously unappreciated diversity in myoepithelial and luminal cell expression. We discover differential expression of Notch ligands DLL1, JAG1, and JAG2 in myoepithelial cells, suggesting a paracrine interaction that may support oncogenic Notch signaling. We further validated this selective expression in three published cohorts of ACC patients. Our data provide a potential explanation for the biphasic nature of low and intermediate grade ACC and may help direct new therapeutic strategies against these tumors.
2022-10-26 | GSE210171 | GEO
Project description:Pluripotent stem cells (PSC) represent an alternative source of hematopoietic stem cells (HSCs). Clinical translation is impeded by limited engraftment of human (h)PSC-multipotent progenitor cells (MPP). This barrier suggests that additional cues are required for definitive hematopoiesis. We hypothesized that vascular niche producing Notch ligands Jagged-1 (JAG1) and Delta-like ligand-4 (DLL4) would drive definitive hematopoiesis. To test our hypothesis, hes2 human embryonic stem cells (hESC) 2 and Macaca nemestrina (Mn) iPSC line-7 were differentiated with cytokines ± endothelial cells (EC), which express JAG1 and DLL4. EC co-culture supported emergence of 8-fold more CD34+CD45+ cells compared to co-culture with cytokines ± ECs with JAG1 or DLL4 knockdown. EC-induced cells exhibit Notch activation and express HSC-specific targets of Notch signaling RUNX1 and GATA2. EC-induced PSC-MPP engraft at a higher level in NSG mice compared to cytokine-induced cells (10% >5 months), and selection increased engraftment (30%). Long-term engraftment and the myeloid-to-lymphoid ratio achieved with vascular niche induction is similar to levels achieved for cord blood MPP and up to 20-fold higher than hPSC-MPP engraftment. Our findings identify a previously underappreciated role for endothelial Notch ligands in PSC definitive hematopoiesis and production of long-term engrafting CD34+ cells and suggest they are critical for HSC emergence. Transcriptome sequencing of Macaca nemestrina (Mn) iPSCs
2015-12-31 | E-GEOD-64644 | biostudies-arrayexpress
Project description:Background: Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process is unknown Results: The objective of this study was to define the role of the Notch ligand JAG1 in regulating BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. Conclusions: These data demonstrate JAG1 mediated Notch signaling regulates differentiation of BC into secretory cells. This study demonstrates that expression of the Notch ligand JAG1 is highly enriched in basal stem/progenitor cells (BC) of the human airway epithelium and that modulation of its expression levels during differentiation of BC play an important role in regulating secretory cell differentiation with no effect on ciliated cell differentiation. These observations have implications for developing novel targets to specifically modulate levels of secretory cells in human airway disorders.
2017-08-23 | GSE76421 | GEO