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A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations

ABSTRACT: A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations

PROVIDER: PRJNA907257 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22478600.fastq.gz	Fastqsanger.gz
	SRR22478601.fastq.gz	Fastqsanger.gz
	SRR22478602.fastq.gz	Fastqsanger.gz
	SRR22478603.fastq.gz	Fastqsanger.gz
	SRR22478604.fastq.gz	Fastqsanger.gz

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

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

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A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [ATAC-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 | GSE219151 | GEO

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A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-03-22 | GSE219153 | GEO

MYCN induces neuroblastoma in primary neural crest cells

Project description:Neuroblastoma (NBL) is an embryonal cancer of the sympathetic nervous system (SNS) that causes 15% of pediatric cancer deaths. High-risk neuroblastoma is characterized by N-Myc amplification and segmental chromosomal gains and losses. Due to limited disease models, the etiology of neuroblastoma is largely unknown, including both the cell of origin and the majority of oncogenic drivers. We have established a novel system for studying neuroblastoma based on the transformation of neural crest cells (NCCs), the progenitor cells of the SNS, isolated from mouse embryonic day 9.5 trunk neural tube explants. Based on pathology and gene expression analysis, we report the first successful transformation of wild-type NCCs into NBL by enforced expression of N-Myc to generate phenotypically and molecularly accurate tumors that closely model human MYCN-amplified NBL. Using comparative genomic hybridization, we found that NCC-derived neuroblastoma tumors acquired copy number gains and losses that are syntenic to those observed in human MYCN-amplified neuroblastoma including 17q gain, 2p gain and loss of 1p36. When p53-compromised NCCs were transformed with N-Myc we generated primitive neuroectodermal tumors with divergent differentiation including osteosarcoma. These subcutaneous tumors were metastatic to regional lymph nodes, liver and lung. Our novel experimental approach accurately models human neuroblastoma and establishes a new system with potential to study early stages of neuroblastoma oncogenesis, to functionally assess neuroblastoma oncogenic drivers, and to characterize neuroblastoma metastasis.

2017-09-25 | GSE94914 | GEO

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