Mus musculus
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ABSTRACT:
PROVIDER: PRJNA150579 | ENA |
REPOSITORIES: ENA
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Project description:Tumor formation constitutes a major obstacle to the clinical application of embryonic stem cells (ESCs). As P-RPCs could successfully integrate into host eyes without development of teratomas or NOG, we sought to identify differentially expressed genes between P-RPCs and ESC-RPCs through genome-wide transcript profiling. Inhibition of Wnt signaling by DKK1 promotes the commitment of ESC-RPCs to more mature retinal cells and reduces the occurrence of NOG to 3%. DKK1-treated ESC-RPCs efficiently integrate to the host retina, form synaptic connections and restore visual function. Here, we report that further differentiation of ESC-derived neural progenitors into retinal progenitor cells (ESC-RPCs) completely eliminates teratomas in ocular transplantation. However, tumor-like neural overgrowth (NOG) occurs in 61% of transplanted eyes.
2013-04-16 | GSE34002 | GEO
Project description:Tumor formation constitutes a major obstacle to the clinical application of embryonic stem cells (ESCs). As P-RPCs could successfully integrate into host eyes without development of teratomas or NOG, we sought to identify differentially expressed genes between P-RPCs and ESC-RPCs through genome-wide transcript profiling. Inhibition of Wnt signaling by DKK1 promotes the commitment of ESC-RPCs to more mature retinal cells and reduces the occurrence of NOG to 3%. DKK1-treated ESC-RPCs efficiently integrate to the host retina, form synaptic connections and restore visual function. Here, we report that further differentiation of ESC-derived neural progenitors into retinal progenitor cells (ESC-RPCs) completely eliminates teratomas in ocular transplantation. However, tumor-like neural overgrowth (NOG) occurs in 61% of transplanted eyes. ESC-RPCs were divided into two groups according to the differentiation stages for RNA extraction and hybridization on Affymetrix microarrays. Normal control ESC-RPCs (N) were represented the homogeneous populations of early stage expression profiles of immature ESC-RPCs. DKK1 treated ESC-RPCs (D) were represented the homogeneous populations of late stage expression profiles of further differetiated mature ESC-RPCs. To sought the pathways involved in the proliferation and oncogenesis of ESC-RPCs, the newborn C57 mice reitinal progenitor cells (R) were applied as negative control. Each group above had three independent biological repeats.
2013-04-16 | E-GEOD-34002 | biostudies-arrayexpress
Project description:Identification of differential expressed genes among P-RPC, rESC-RPC1 and rESC-RPC2 through genome-wide transcript profiling
| PRJNA279270 | ENA
Project description:Successful embryonic development depends upon molecules secreted by the reproduc-tive tract. Among such molecules is dickkopf 1 (DKK1), an canonical WNT antagonist that can also activate the planar cell polarity (PCP) pathway. Objectives were to determine whether DKK1 regulates expression of genes that promote differentiation, possibly through the PCP pathway, and to determine if actions of DKK1 on the embryonic transcriptome were dependent on embryo sex. Bovine oocytes were fertilized with pools of X- or Y-sorted sperm. Embryos were treated with 100 ng/ml DKK1 or vehicle at Day 5 of development and harvested 24 h later for microarray analysis of global gene expression. A total of 9,931 transcripts were identified as being expressed. with124 being differentially expressed genes between females and males. A total of 68% of the genes upregulated in females were located on the X chromosome. DKK1 changed expression of 132 genes in females and 136 in males. Of these, 34 genes were regulated by DKK1 in both sexes - 14 in the same direction and 20 in opposite directions. Evidence for regulation of the PCP pathway by DKK1 was the finding that DKK1 regulated expression of genes involved in cell polarization and differentiation in both females and males. In both sexes, DKK1 regulated expression of many genes associated with HNF4A, a marker of hypoblast cells that promotes formation of cell junctions. In conclusion, DKK1 regulates cell differentiation and embryonic development in a sex-dependent manner and effects may be mediated, at least in part, by activation of the PCP pathway. Bovine embryos produced with X- or Y-sorted sperm were cultured in vitro and treated with vehicle or DKK1 at day 5 of development and harvested at day 6 for RNA isolation, amplification and hibridization to Affymetrix Bovine Gene 1.0 ST arrays. The study was done in 5 replicates using pools of 20 morulae for each treatment.
2014-08-06 | E-GEOD-60098 | biostudies-arrayexpress
Project description:Sex affects function of the developing mammalian embryo as early as the preimplantation period. There were two goals of the current objective. The first was to determine the degree and nature of differences in gene expression between female and male embryos in the cow at the morula stage of development. The second objective was to determine whether DKK1, a molecule known to alter differentiation of the blastocyst, would affect gene expression differently for female and male morulae. In Experiment 1, female and male embryos were treated with DKK1 at Day 5 after insemination. Morulae were harvested 24 h after treatment, pooled in groups of 20 for microarray analysis and RNA subjected to analysis of gene expression by microarray hybridization. There were 662 differentially expressed genes between females and males and 128 of these genes had a fold change ≥ 1.5 between the two sexes. Of the genes upregulated in females, 49.5% were located in the X chromosome. Functional analysis predicted that cell survival was greater in female embryos. Experiment 2 involved a similar design except that transcripts for 12 genes previously reported to be affected by sex, DKK1 or the interaction were quantified by quantitative polymerase chain reaction. Expression of all genes tested that were affected by sex in experiment 1 was affected in a similar manner in Experiment 2. In contrast, effects of DKK1 on gene expression were largely not repeatable in Experiment 2. The exception was for the Hippo signaling gene AMOT, which was inhibited by DKK1. In Experiment 3, embryos produced by fertilization with unsorted sperm were treated with DKK1 at Day 5 and abundance of transcripts for CDX2, GATA6, and NANOG determined at Days 5, 6 and 7 after insemination. There was no effect of DKK1 on expression of any of the three genes. In conclusion, female and male bovine embryos have a different pattern of gene expression as early as the morula stage, and this is due to a large extent to expression of genes in the X chromosomes in females. Differential gene expression between female and male embryos is likely the basis for increased resistance to cell death signals in female embryos and disparity in responses of female and male embryos to changes in the maternal environment.
2014-08-06 | GSE60098 | GEO
Project description:Dickkopf 1 (DKK1) could promote tumor progression by suppressing immunity. Therefore, we investigated whether DKK1 influence prognosis and sensitivity to PD-1 blockade in colorectal cancers (CRCs) with defective DNA mismatch repair genes (dMMR) or microsatellite instability (MSI). We found that elevated DKK1 expression was associated with recurrence and dismissed CD8+ T cell infiltrations, and patients with high serum DKK1 had poor anti-PD-1 response. RNA interference or neutralization of DKK1 in CRCs enhanced CD8+ T cell cytotoxicity, and down-regulation of T-bet and E2F1 following GSK3β activation was detected in DKK1-treated CD8+ T cells. In organoid-lymphocyte co-culture model, apoptosis proportions were elevated after individual neutralization of both PD-1 and DKK1, and the combined neutralization resulted in further increases. In conclusion, DKK1 suppresses tumor immunity in dMMR/MSI CRCs by inactivating CD8+ T cells through GSK3β/E2F1/T-bet axis. DKK1 neutralization may improve the sensitivity to PD-1 blockade in dMMR/MSI CRCs.
2021-04-07 | GSE149206 | GEO
Project description:Efficient and sustained knockdown of DNMT1 transcript and protein was achieved using a consecutive transfection protocol in the mouse pituitary adenoma cell line, AtT-20. Genome wide microarray analysis identified 91 transcripts that were significantly differentially expressed relative to cells treated with a non-targeting control. Keywords: Differential expression
2008-12-31 | GSE10552 | GEO
Project description:Degenerative retinal diseases like age-related macular degeneration (AMD) are the leading cause of blindness. Cell transplantation showed promising therapeutic effect for such diseases, and retinal progenitor cell (RPC) derived from embryonic stem cell (ESC) is one of the sources of such donor cells. Here, we established two protocols through which two types of rat ESC-derived RPCs (rESC-RPCs) were obtained and both contained some NPCs and committed retina lineage cells. As P-RPCs have been reported to successfully integrate into host eyes, we sough to identify differentially expressed genes among P-RPCs, rESC-RPC1s and rESC-RPC2s through genome-wide transcript profiling. rESC-RPC2 can integrate into the host retina, form synaptic connections and restore visual function after transplanted into the degenerative retinal disease model RCS rat.
2015-10-01 | GSE67213 | GEO
Project description:Infection with oncogenic human papillomavirus (HPV) is a major cause for the development of cervical cancer, which is mainly driven by the expression of the HPV E6 and E7 oncoproteins. We uncovered that the concentration levels of the putative tumor suppressor Dickkopf-1 (Dkk1) are restricted in cervical cancer cells by HPV E6 expression due to the E6-mediated proteolytic degradation of p53, which is a transcriptional regulator of Dkk1. Moreover, we found that Dkk1 is critically involved in the pro-apoptotic Cisplatin response of these cells, as Dkk1 repression was associated with an increased resistance towards the chemotherapeutic compound. This could be of high relevance for cervical cancer treatments, which usually involve Cisplatin for standard care. Although Dkk1 is a major antagonist of the canonical Wnt signaling, the differential response towards Cisplatin observed in Dkk1-depleted cells was not associated to an activation of this pathway. To elucidate alternative underlying mechanisms, we performed Affymetrix Gene Expression analyses comparing the transcriptome of Cisplatin-treated parental HeLa to CRISPR/Cas9-generated Dkk1 knockout (KO) HeLa cells. These revealed that Dkk1 depletion is linked to an impairment of the pro-apoptotic JNK/AP-1 pathway in cervical cancer cells, suggesting that Dkk1 drives Cisplatin-mediated apoptosis via activation of this signaling hub.
2022-08-16 | GSE200748 | GEO
Project description:Canonical Wnt signaling controls proliferation and differentiation of osteogenic progenitor cells, and tumor-derived secretion of the Wnt antagonist Dickkopf-1 (Dkk1) is correlated with osteolyses and metastasis in many bone malignancies. However, the role of Dkk1 in the oncogenesis of primary osteosarcoma (OS) remains unexplored. Here, we over-expressed Dkk1 in the OS cell line MOS-J. Contrary to expectations, Dkk1 had autocrine effects on MOSJ cells in that it increased proliferation and resistance to metabolic stress in vitro. In vivo, Dkk1 expressing MOS-J cells formed larger and more destructive tumors than controls. These effects were attributed in part to up-regulation of the stress response enzyme and cancer stem cell marker aldehyde-dehydrogenase-1 (ALDH1) through Jun-N-terminal kinase signaling. This is the first report linking Dkk1 to tumor stress resistance, further supporting the targeting of Dkk1 not only to prevent and treat osteolytic bone lesions but also to reduce numbers of stress-resistant tumor cells. Two samples were analyzed, one human DKK1 transfected MOS-J cell sample and one control vector transfected MOS-J cell sample.
2012-12-22 | E-GEOD-43112 | biostudies-arrayexpress