ScRNAseq in a panel of neuroblasoma cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE229224 | GEO | 2023/04/10
REPOSITORIES: GEO
Similar Datasets
Project description:Polo-Like Kinase 1 (PLK1), a serine/threonine kinase involved in cell cycle regulation at the G2/M transition, is associated with high-risk neuroblastoma (NB) and unfavorable patient outcome. Recently, we and others demonstrated that PLK1 is a potential drug target in neuroblastoma and reported antitumoral actvity of the PLK1 inhibitor BI2536 in preclinical models of NB. We here analyzed the effects of the ATP-competitive PLK1 inhibitor GSK461364 on typical tumorigenic properties of preclinical in vitro and in vivo models of NB. Treatment of NB cells with GSK461364 resulted in decreased cell viability and reduction of proliferative capacity, and led to cell cycle arrest and massive induction of apoptosis. These phenotypic consequences were observed at low-dose nanomolar levels and were independent of the MYCN copy number status of the cell lines. In vivo treatment with GSK461364 led to a strong delay in tumor development and to a highly significant increase in survival in the treatment group. These preclinical findings highlight the promise of PLK1 inhibitors as novel agents for NB and serve as rationale to move forward with early phase clinical trials in children.
2015-03-21 | GSE67102 | GEO
Project description:Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of about 50%. The multimodal therapeutic scheme of NB includes isotretinoin (13cRA), used in the post-consolidation phase as an anti-proliferative and pro-differentiative agent to minimize residual disease and prevent relapse. Through a small molecule screening, we identified isorhamnetin (ISR) as a synergistic compound with 13cRA in inhibiting up to 80% of NB cell viability. To unveil the molecular mechanisms underlying this synergism, microarray analysis was performed in CHP134 control cells, and cells treated with 13cRA (5uM), ISR (15uM), and their combination. This analysis revealed that 13cRA ISR synergism is accompanied by a marked increase in the expression of the adrenergic receptor α1B (ADRA1B) gene. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, with 13cRA in NB xenografted mice exerted a marked control of tumor growth, while each of the two drugs alone was ineffective. We, therefore, preclinically identify the α1B adrenergic receptor as a novel pharmacological target in NB. We propose evaluating the addition of α1-antagonists in the post-consolidation therapy of NB to more efficiently control residual disease. Keywords: isotretinoin, 13cRA, 13-cis retinoic acid, isorhamnetin, ISR, neuroblastoma, polysome profiling, translatome, adrenergic receptors, α-blockers, combinatorial therapy, synergy
2023-05-29 | GSE232388 | GEO
Project description:The initiation of drug response in neuroblastoma was assessed using this genetically engineered mouse model. scRNAseq was employed to determine the heterogeneity of the initial transcriptional response to the common chemotherapeutic drug, cisplatin.
2023-04-10 | GSE229226 | GEO
Project description:Human induced pluripotent stem cell-derived kidney organoids have potential for disease modelling and regenerative medicine purposes. However, they lack a functional vasculature and remain immature in in vitro culture. Here, we transplanted kidney organoids at day 7+12 of differentiation in the coelomic cavity of chicken embryos and then compared them to their respective untransplanted controls at d7+13 and d7+20 using scRNAseq and imaging modalities. We demonstrate vascularization and enhanced maturation of transplanted kidney organoids.
2022-08-05 | E-MTAB-11429 | biostudies-arrayexpress
Project description:Background: Although most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapy strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican (GPC)2 and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation. Methods: We evaluated different GPC2-CAR constructs by measuring the CAR activity against several NB cell lines in vitro. NOD-SCID mice engrafted with human NB cell lines or orthotopic patient-derived xenograft (PDX) and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing. Results: Applying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR backbone with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain elicits the best preclinical anti-NB activity compared to other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8+ effector T cells in the tumor-microenvironment and upregulation of several effector molecules such as GNLY, GZMB, ZNF683, and HMGN2. Finally, we also showed that the CT3.28H.BBζ CAR was more potent than a recently clinically tested GD2-targeted CAR to control NB in vivo. Conclusion: Given the robust preclinical activity of CT3.28H.BBζ, these promising results warrant further clinical testing in children with NB.
2023-01-18 | GSE212658 | GEO
Project description:scRNAseq in a panel of neuroblasoma cell lines
| PRJNA953425 | ENA
Project description:<p>Neuroblastoma is the most common extra-cranial solid tumor in children. It represents 8% to 10% of all childhood cancers. Stage 4 Neuroblastoma is characterized by its clinical heterogeneous outcome. The special category, stage 4S tumors (2-5% of all NB) are chemo-sensitive, and the patients show spontaneous regression. On the other hand, MYCN amplification (25-30% of all NB) is associated with poor outcome of neuroblastoma, thus we further categorize stage 4 neuroblastoma into MYCN non-amplified and MYCN amplified group. Here we use transcriptome sequencing to characterize the transcriptome in 29 stage 4 Neuroblastoma samples.</p>
| phs000868 | dbGaP
Project description:Neuroblastoma (NB) is an aggressive childhood tumor, with high-risk cases having a 5-year overall survival probability of about 50%. The multimodal therapeutic scheme of NB includes isotretinoin (13cRA), used in the post-consolidation phase as an anti-proliferative and pro-differentiative agent to minimize residual disease and prevent relapse. Administration of doxazosin, a safe α1-antagonist used in pediatric patients, with 13cRA in NB xenografted mice exerted a marked control of tumor growth, while each of the two drugs alone was ineffective. To unveil the molecular mechanisms underlying this synergism, single-cell RNA-seq was performed in CHP134 control cells, and cells treated with 13cRA (5 uM), doxazosin (10 uM), and their combination. The data revealed that the transcriptome of single cells was markedly reprogrammed when exposed to 13cRA and to the combination of doxazosin and 13cRA, but not when exposed to doxazosin alone. In detail, we identified 91 genes as specific markers of 307 cells treated with the drug combination: 41 synergistically downregulated and 50 upregulated. Functional analysis of these synergistically expressed genes reported significant enrichment of genes related to apoptosis, control of the cell cycle, and neuronal identity. We, therefore, preclinically identify the α1B adrenergic receptor as a novel pharmacological target in NB. We propose evaluating the addition of α1-antagonists in the post-consolidation therapy of NB to more efficiently control residual disease. Keywords: isotretinoin, 13cRA, 13-cis retinoic acid, doxazosin, neuroblastoma,single-cell RNA-seq, iCELL8, adrenergic receptors, α-blockers, combinatorial therapy, synergy
2023-05-29 | GSE232498 | GEO
Project description:Neuroblastoma (NB) is a devastating childhood cancer that remains clinically unmet. There is an urgency to develop new approaches to treat the disease. Protein arginine methyltransferase (PRMT5) is over-expressed in a wide variety of cancers and has been implicated with a key oncogenic role, achieved in part through its control of the master transcription regulator E2F1. Here, we have investigated the relevance of the interplay between PRMT5 and E2F1 in neuroblastoma and found that elevated expression occurs in poor prognosis high-risk disease. Cell lines derived from NB that recapitulate high PRMT5 and E2F1 expression exhibit increased levels of alternative RNA splicing compared to their low expression cell counterparts. Cancer-relevant exon-skipping events in apoptotic genes were apparent in high expressing NB cells which resulted in protein isoforms with decreased apoptotic activity. Pharmacological inhibition of PRMT5 or inactivation of E2F1 activity reduced exon skipping and reinstated normal apoptotic activity. Our findings show that a cancer relevant alternative splicing programme desensitises high risk NB to apoptosis. The critical role ascribed to PRMT5 and E2F1 in attaining the alterative RNA splicing programme equally identifies PRMT5 as a potential therapeutic target for neuroblastoma disease.
2024-09-14 | GSE243989 | GEO
Project description:ALK is a tyrosine kinase receptor and oncogene in neuroblastoma (NB). The receptor is activated by the ALKAL2 ligand, but it is unknown whether missregulation of this ligand may play a role in NB carcinogenesis. To characterize the transcriptomic response to ALKAL2 in neuroblastoma cell lines, RNA-Seq was performed on NB1 and IMR32 human NB cell lines.
2020-11-24 | E-MTAB-9598 | biostudies-arrayexpress