Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-omics analysis of neuroblastoma cells reveals a diversity of malignant transformations

ABSTRACT: Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system that exhibits significant variation in the stage of differentiation and cell composition of tumours. Global loss of DNA methylation and genomic 5-hydroxymethylcytosine (5hmC) is a hallmark of human cancers. Here, we used our recently developed single base resolution approaches, hmTOP-seq and uTOP-seq, for construction of 5hmC maps and identification of large hypomethylated domains (PMDs) in different NB cell subpopulations. The 5hmC profiles revealed distinct signatures characteristic of different cell lineages and stages of malignant transformation of NB cells in a conventional and oxygen depleted environment, which often occurs in tumours. The analysis of the cell type-specific PMD distribution highlighted differences in global genome organization among NB cells that were ascribed to the same lineage identity by transcriptome assays. Collectively, we demonstrated a high informativeness of the integrative epigenomic and transcriptomic research in relation to large scale genome structure in investigating the mechanisms that regulate cell identities and developmental stages of NB cells. Such multi-omics analysis, as compared to mutational studies, open new ways for identification of novel disease-associated features which bring prognostic and therapeutic value in treating this aggressive pediatric disease.

ORGANISM(S): Homo sapiens

PROVIDER: GSE130612 | GEO | 2021/08/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Characterization of universal features of partially methylated domains across tissues and species

Project description:Partially methylated domains (PMDs) are a hallmark of epigenomes in reproducible and specific biological contexts, including cancer cells, the placenta, and cultured cell lines. Existing methods for deciding whether PMDs exist in a sample, as well as their identification, are few, often tailored to specific biological questions, and require high coverage samples for accurate identification. In this study, we outline a set of axioms that take a step towards a functional definition for PMDs, describe an improved method for comparable PMD detection across samples with substantially different sequencing depths, and refine the decision criteria for whether a sample contains PMDs using a data-driven approach. Applying our method to 267 methylomes from 7 species, we corroborated recent results regarding the general association between replication timing and PMD state, and report identification of several reproducibly “escapee” genes within late-replicating domains that escape the downregulation and hypomethylation of their immediate genomic neighborhood. We also explored the discordant PMD state of orthologous genes between human and mouse, and observed a directional association of PMD state with gene expression and local gene density. Our improved method makes low-sequencing, population-level studies of PMD variation possible and our results further refine the model of PMD formation as one where sequence context and regional epigenomic features both play a role in gradual genome-wide hypomethylation.

2020-09-27 | GSE152819 | GEO

Large-scale methylation domains mark a functional subset of neuronally expressed genes

Project description:DNA methylation is essential for embryonic and neuronal differentiation, but the function of most genomic DNA methylation marks are poorly understood. Generally the human genome is highly methylated (>70%) except for CpG islands and gene promoters. However, it was recently shown that the IMR90 human fetal lung fibroblast cells have large regions of the genome with partially methylated domains (PMDs, <70% average methylation), in contrast to the rest of the genome which is in highly methylated domains (HMDs, >70% average methylation). Using bisulfite conversion followed by high-throughput sequencing (MethylC-seq), we discovered that human SH-SY5Y neuronal cells also contain PMDs. We developed a novel hidden Markov model (HMM) to computationally map the genomic locations of PMDs in both cell types and found that autosomal PMDs can be over 9 Mb in length and cover 41% of the IMR90 genome and 19% of the SH-SY5Y genome. Genomic regions marked by cell line specific PMDs contain genes that are expressed in a tissue-specific manner, with PMDs being a mark of repressed transcription. Genes contained within N-HMDs (neuronal HMDs, defined as a PMD in IMR90 but HMD in SH-SY5Y) were significantly enriched for calcium signaling, synaptic transmission and neuron differentiation functions. Autism candidate genes were enriched within PMDs and the largest PMD observed in SH-SY5Y cells marked a 10 Mb cluster of cadherin genes with strong genetic association to autism. Our results suggest that these large-scale methylation domain maps could be relevant to interpreting and directing future investigations into the elusive etiology of autism. Examined DNA methylation in a human neuronal cell line and cerebral cortex

2011-06-23 | E-GEOD-25930 | biostudies-arrayexpress

Large-scale methylation domains mark a functional subset of neuronally expressed genes

2011-06-23 | GSE25930 | GEO

The effects of postmortem delay on mouse microglia gene expression

Project description:Microglia are specialized macrophages of the central nervous system (CNS) and first to react to pathogens or injury. Transcriptional profiling significantly contributed to our understanding of microglia functions. In the case of human CNS samples, a postmortem delay (PMD) in tissue access and collection is the potential factor that might affect microglia gene expression profiles. However, the direct analysis of effects of PMD on human microglia transcriptome is challenging due to many confounding factors such as sex, aging, nutrition, lifestyle, medication and medical history. To determine the effects of PMD on the microglia transcriptome. Here, we analyzed mouse microglia, where ante-mortem conditions and post-mortem delay can be tightly controlled. PMD had very limited effect on mouse microglia gene expression, only 50 genes (out of 15,554 detected genes) were differentially expressed between different PMDs.

2021-01-01 | GSE162209 | GEO

ATR inhibition enables complete tumour regression in ALK-driven NB mouse models

Project description:High-risk neuroblastoma (NB) often involves amplification of the neural MYC (MYCN) oncogene as well as mutations in ALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes such as MYCN and ALK result in increased replication stress in cancer cells, offering one such therapeutically exploitable option. Here, we followed up on earlier phosphoproteomic analyses that identified ATR activity in ALK-driven NB cell lines. We tested several ATR inhibitors, identifying BAY 1895344 as the most potent inhibitor of NB cell growth and proliferation. Using RNA-Seq, proteomics and phosphoproteomics we characterized the response of NB cells and tumours to ATR inhibition, identifying key components of the DNA damage response (DDR) as well as ATRX, MYCN, E2F and DCK among other ATR targets in NB cells. ATR inhibition with BAY 1895344 also produced robust responses in mouse NB models. Remarkably, a 2 week protocol combining ATR and ALK inhibition led to complete regression of NB tumours in two independent NB genetically modified mouse tumour models. These results suggest that NB patients, particularly in high-risk groups with oncogene induced replication stress, may benefit from inhibition of ATR as therapeutic intervention.

2021-11-02 | PXD027187 | Pride

Epigenetic dynamics of 5-hydroxymethylcytosine during mouse spermatogenesis

Project description:Studies on the epigenetic regulation of gene expression during germ cell development are still at the beginning stage. In the present study, we used our highly specific 5hmC-labeling and enrichment technique coupled with DNA deep-sequencing to profile the global 5hmC distribution in 8 serial stages of male germ cells during spermatogenesis, as well as in the the Sertoli cells (SE) which are the only somatic cell type inside seminiferous tubules. We analyzed the genomic distribution and dynamic changes of 5hmC during spermatogenesis. Moreover, to dissect the functional significance of 5hmC modifications for transcriptional regulation of gene expression, we also performed RNA-Seq transcriptome analysis in all of the 8 corresponding stages of male germ cells and found that 5hmC is positively correlated with gene expression. RNA-seq: Examination of the transcriptomes during mouse spermatogenesis. 5hmC-seq: Identification of 5hmC enriched genmoic regions in mouse germ cell.

2012-03-12 | E-GEOD-35005 | biostudies-arrayexpress

Transcription profiling of human pediatric solid tumor cell lines

Project description:For identification of candidate genes that is specifically expressed in Ewing family tumor (EFT) cells, we performed DNA microarray-based global expression profiling using Affymetrix Human Genome U133 Plus 2.0 Array and analyxed expression profiles from EFT cell lines (7 lines), neuroblastoma (NB) cell lines (3 lines), a Rhabdomyosarcoma (RMS) cell line, and a human immortalized mesenchymal progenitor cells UET-13 cells. Experiment Overall Design: Expression profiles of pediatric solid tumor cell lines were analyzed and compared using Affymetrix HG-U133 Plus 2.0 (GPL570).

2008-06-16 | E-GEOD-8596 | biostudies-arrayexpress

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [10x scRNA-seq]

Project description:Early childhood tumours arise from transformed embryonic cells, which often carry large copy number alterations (CNA). However, it remains unclear how CNAs contribute to embryonic tumourigenesis due to a lack of suitable models. Here we employ female human embryonic stem cell (hESC) differentiation and single-cell transcriptome and epigenome analysis to assess the effects of chromosome 17q/1q gains, which are prevalent in the embryonal tumour neuroblastoma (NB). We show that CNAs impair the specification of trunk neural crest (NC) cells and their sympathoadrenal derivatives, the putative cells-of-origin of NB. This effect is exacerbated upon overexpression of MYCN, whose amplification co-occurs with CNAs in NB. Moreover, CNAs potentiate the pro-tumourigenic effects of MYCN and mutant NC cells resemble NB cells in tumours. These changes correlate with a stepwise aberration of developmental transcription factor networks. Together, our results sketch a mechanistic framework for the CNA-driven initiation of embryonal tumours.

2024-03-22 | GSE221853 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [ATAC-seq]

2024-03-22 | GSE219151 | GEO

A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [RNA-seq]

2024-03-22 | GSE219149 | GEO