Dataset Information

Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing of neuroblastoma cell lines

ABSTRACT: This study was undertaken to assess transcriptional and epigenetic heterogeneity a the level of individual cells within neuroblastoma cell lines, and to compare cell lines with MYCN amplificaion to cell lines without MYCN amplification. Methods: We used 10X Genomics multiome sequencing technology to perform joint gene expression and ATAC profiling on thousands of nuclei isolated from the following human neuoblastoma cell lines: SHSY5Y, SK-N-AS, SK-N-SH, SK-N-DZ, Be-2c, and CHP134. Results: We found considerable gene expression and epigeneic heterogeneity both within and between neuroblastoma cell lines. Conclusion: Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing has demonsrated that neuroblastoma cell lines are heterogeneous, which may have implications for therapeutic strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262189 | GEO | 2024/09/17

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with diverse clinical behaviors. Even with multimodal therapies, high-risk neuroblastoma has an unfavorable outcome irrespective of MYCN amplification, a well-established oncogenic driver in neuroblastoma pathogenesis, and its genetic heterogeneity has largely impeded efforts to correlate molecular targets with biological consequences for more effective treatment strategies. Here, using a gene expression-based approach, we identified the FDA-approved anthelmintic niclosamide as a potential anti-neuroblastoma drug. By combining the gene expression signature associated with high-risk neuroblastoma and the recurrent drug−transcript relationships inferred from up to one million perturbational gene expression profiles, our algorithm predicted effective therapeutic candidates by evaluating the extent to which a given compound or their combinations could ‘reverse’ the high-risk signature. Furthermore, we performed quantitative polymerase chain reaction (qPCR) to validate top five candidate reverse genes which are involved in DNA replication, including cyclin A2 (CCNA2), minichromosome maintenance 10 replication initiation factor (MCM10), ERCC excision repair 6 like, spindle assembly checkpoint helicase (ERCC6L), kinesin family member 20A (KIF20A), and RuvB like AAA ATPase 1 (RUVBL1). Indeed, those five genes were downregulated in niclosamide-treated cells, indicating niclosamide suppressed DNA replication and then inhibited cell proliferation. Using cell proliferation and clonogenic assays as well as flow cytometry, we determined the cytotoxic effects of niclosamide in MYCN-amplified SK-N-DZ and non-amplified SK-N-AS cells. The results showed that niclosamide could effectively reduce not only cell proliferation and colony formation but also trigger cell cycle arrest and apoptosis. Moreover, we conducted human tumor xenografts in a nude mice model to evaluate the in vivo efficacy of niclosamide and found that it significantly suppressed tumor growth and prolonged survival rate, but doesn’t cause organ damage and change body weight. To explore the molecular mechanism of niclosamide, stable-isotope dimethyl labeling strategy for quantitative proteomics was performed on both cell-based or xenograft-based MYCN-amplified SK-N-DZ and MYCN-nonamplified SK-N-AS models. We confirmed niclosamide not only mediated the function of mitochondrial electron transport chain but also the other functions in high risk neuroblastoma cell lines and xenografts. The results suggest that our developed expression-based strategy is useful for drug discovery and provides the possibility of repurposing the anthelminthic drug niclosamide for treating high-risk neuroblastoma therapy.

Dataset Information

Joint single-nucleus RNA sequencing and single-nucleus ATAC sequencing of neuroblastoma cell lines

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets