Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA320772 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Small cell lung cancer (SCLC) tumors harbor two subsets of cells that are defined by low (or undetectable) or high expression of Hes1, which is a common downstream target of the Notch signaling pathway. To better understand the role of the Notch pathway in SCLC tumor heterogeneity, we first isolated cells from these two populations using a GFP-reporter allele for Hes1 expression. We then used microarrays to identify the gene expression differences between these two groups.
2017-04-21 | GSE81170 | GEO
Project description:High levels of Hes1 expression are frequently found in BCR-ABL-positive chronic myelogenous leukemia in blast crisis (CML-BC). In mouse bone marrow transplantation (BMT) models, co-expression of BCR-ABL and Hes1 induces CML-BC–like disease; however the underlying mechanism remained elusive. Here, based on gene expression analysis, we show that MMP-9 is upregulated by Hes1 in common myeloid progenitors (CMPs). Analysis of promoter activity demonstrated that Hes1 upregulated MMP-9 by activating NF-kB. Analysis of 20 samples from CML-BC patients showed that MMP-9 was highly expressed in three, with two exhibiting high levels of Hes1 expression. Interestingly, MMP-9 deficiency impaired the cobblestone area-forming ability of CMPs expressing BCR-ABL and Hes1 that were in conjunction with a stromal cell layer. In addition, these CMPs secreted MMP-9, promoting the release of soluble Kit-ligand (sKitL) from stromal cells, thereby enhancing proliferation of the leukemic cells. In accordance, mice transplanted with CMPs expressing BCR-ABL and Hes1 exhibited high levels of sKitL as well as MMP-9 in the serum. Importantly, MMP-9 deficiency impaired the development of CML-BC–like disease induced by BCR-ABL and Hes1 in mouse BMT models. The present results suggest that Hes1 promotes the development of CML-BC, partly through MMP-9 upregulation in leukemic cells. Common myeloid progenitors (CMPs; Lineage negative, c-Kit positive, Sca-1 negative, Fc-gamma-receptor low, CD34 positive fraction) were sorted with a FACSAria cell sorter (Becton Dickinson). Retroviruses were generated by transfecting Plat-E packaging cells with retrovirus vector pMYs-Hes1-IRES-GFP or empty vector (pMYs-IRES-GFP) using FuGENE 6 (Roche Diagnostics). Infection of retrovirus harboring Hes1 (pMYs-Hes1-IRES-GFP) or empty vector (pMYs-IRES-GFP) into progenitors was performed using RetroNectin (Takara Bio). Hes1-transfected CMPs and Mock-transduced CMPs were isolated 36 hours after infection with a FACSAria cell sorter. One sample of Hes1-transfected CMPs and one sample of mock-transduced CMPs were analyzed with GeneChip Mouse Genome 430 2.0 Array.
2014-05-01 | E-GEOD-56921 | biostudies-arrayexpress
Project description:To identify genome-wide, direct targets of HES1 in human pancreas progenitors, we performed Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) of endogenous HES1 in the HUES4 PDX1GFP/+ reporter cell line on Day 13 of differentiation from both unsorted bulk populations and FACS-sorted GFP+ cells.
2022-02-27 | E-MTAB-6922 | biostudies-arrayexpress
Project description:We report the application of RNA-sequencing for high-throughput profiling of gene expression in hedgehog-responsive stromal cells in normal mouse prostate and mouse prostate tumors. By using the Gli1-GFP knock-in reporter mouse line, we isolated the subset of mouse prostate stromal cells undergoing hedgehog signaling to compare the transcriptomes between PB-MYC prostate tumor and normal prostate in mice at the age of about 45 weeks.
2016-12-14 | GSE92301 | GEO
Project description:Expression data from adult LSK Hes1-GFP positive and adult LSK Hes1-GFP negative
| PRJNA202200 | ENA
Project description:Small-cell lung carcinoma (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) are high-grade lung neuroendocrine tumors (NET). However, comparative protein expression within SCLC and LCNEC remains unclear. Here, protein expression profiles were obtained via mass spectrometry-based proteomic analysis.
2019-05-14 | PXD013583 | JPOST Repository
Project description:Small cell lung cancer is the most aggressive type of lung cancer and has a high degree of plasticity, characterized by a remarkable response to chemotherapy followed by development of resistance. We show that intratumoral heterogeneity of SCLC is progressively established, indicated by the appearance of YAP+ and HES1+ SCLC tumor cells. Notch signaling is required for the generation of Non-NE SCLC cells, but not for the tumorigenesis of SCLC. Furthermore, YAP signals through Notch-dependent and independent pathway to induce REST expression to promote the conversion of NE to Non-NE SCLC tumor cells. In addition, YAP activation enhances the chemoresistance in NE SCLC tumor cells by downregulating GSDME, while inactivation of YAP in Non-NE SCLC tumor cells switches cell death from apoptosis to pyroptosis. Our study will not only provide novel insights into the molecular basis of SCLC tumorigenesis, but also the potential drug targets for SCLC therapy
2021-06-01 | GSE161741 | GEO
Project description:Small cell lung cancer is the most aggressive type of lung cancer and has a high degree of plasticity, characterized by a remarkable response to chemotherapy followed by development of resistance. We show that intratumoral heterogeneity of SCLC is progressively established, indicated by the appearance of YAP+ and HES1+ SCLC tumor cells. Notch signaling is required for the generation of Non-NE SCLC cells, but not for the tumorigenesis of SCLC. Furthermore, YAP signals through Notch-dependent and independent pathway to induce REST expression to promote the conversion of NE to Non-NE SCLC tumor cells. In addition, YAP activation enhances the chemoresistance in NE SCLC tumor cells by downregulating GSDME, while inactivation of YAP in Non-NE SCLC tumor cells switches cell death from apoptosis to pyroptosis. Our study will not only provide novel insights into the molecular basis of SCLC tumorigenesis, but also the potential drug targets for SCLC therapy
2021-06-01 | GSE161740 | GEO
Project description:Methylation is closely involved in the development of various carcinomas. However, little datasets are available for small cell lung carcinoma (SCLC) due to the scarcity of fresh tumor samples. The aim of this study is to investigate the comprehensive genome-wide methylation profile of SCLC to predict the prognosis after surgical treatment. We investigated the high DNA methylated and low gene expression sites using 25 SCLC tumor tissues. First, we selected most differentially methylated CpG sites across the tumor tissues. Following hierarchical clustering (HC) and non-negative matrix factorization (NMF), gene ontology analysis was performed using DAVID software. Clustering of SCLC tumors led to the important identification of a CpG island methylator phenotype (CIMP) of SCLC, and showed that CIMP-high tumors had a significantly poorer prognosis (p = 0.001). Multivariate analysis revealed that postoperative chemotherapy, low neuroendocrine expression and the CIMP-low state were significantly good prognostic factors. Association analyses of methylation and gene expression provided 46 genes with significant correlation. Ontology studies to these genes showed that genes involved in extrinsic apoptosis pathway were suppressed, including TNFRSF1A, TNFRSF10A and TRADD, in CIMP-high tumors, prognosis of which was poorer. By comprehensive DNA methylation profiling, two distinct subgroups were identified to evoke a CIMP of SCLC as a useful marker for determination of treatment. Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for the treatment of an aggressive subtype of SCLC. Comprehensive genome-wide methylation analyses
2014-10-04 | E-GEOD-62021 | biostudies-arrayexpress
Project description:The goal of this study was to characterize and classify pulmonary neuroendocrine tumors based on Array Comparative Genomic Hybridization (aCGH). Using aCGH, we performed karyotype analysis of 33 small cell lung cancer (SCLC) tumors, 13 SCLC cell lines, 19 bronchial carcinoids, and 9 gastrointestinal (GI) carcinoids. In contrast to the relatively stable karyotypes of carcinoid tumors, the karyotypes of SCLC tumors and cell lines were highly aberrant. High copy number (CN) gains were detected in SCLC tumors and cell lines in cytogenetic bands encoding JAK2, FGFR1, and MYC family members. In some of those samples, the CN of these genes exceeded 100, suggesting that they could represent driver alterations and potential drug targets in subgroups of SCLC patients. Recurrent CN alterations of a total of 203 genes, including the RB1 gene, and 59 microRNAs, most of which locate in the DLK1-DIO3 domain, were observed in SCLC tumors, bronchial carcinoids and carcinoids of GI origin; in contrast, CN alterations of the TP53 gene and the MYC family members were observed more frequently in SCLC. These findings suggest the existence of partially shared tumor-specific CN alterations in these tumors. Furthermore, we demonstrated that the aCGH profile of SCLC cell lines highly resemble that of clinical SCLC specimens. Finally, by analyzing potential drug targets, we provide a genomics based rationale for targeting the AKT-mTOR and apoptosis pathways in SCLC. Carcinoids, including 19 bronchial carcinoids and 9 carcinoid of gastrointestinal origin, and small cell lung cancer, including 33 patients' tumor samples and 13 cell line samples, were compared.
2010-04-22 | E-GEOD-21468 | biostudies-arrayexpress