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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE219153 | GEO | 2024/03/22

REPOSITORIES: GEO

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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

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 [Parse scRNA-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

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

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

Project description: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 [ATAC-seq]

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

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

Project description:A human neural crest model reveals the developmental impact of neuroblastoma-associated chromosomal aberrations [Parse scRNA-seq]

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

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

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The connections between neural crest development and neuroblastoma.

Project description:Neuroblastoma (NB), the most common extracranial solid tumor in childhood, is an extremely heterogeneous disease both biologically and clinically. Although significant progress has been made in identifying molecular and genetic markers for NB, this disease remains an enigmatic challenge. Since NB is thought to be an embryonal tumor that is derived from precursor cells of the peripheral (sympathetic) nervous system, understanding the development of normal sympathetic nervous system may highlight abnormal events that contribute to NB initiation. Therefore, this review focuses on the development of the peripheral trunk neural crest, the current understanding of how developmental factors may contribute to NB and on recent advances in the identification of important genetic lesions and signaling pathways involved in NB tumorigenesis and metastasis. Finally, we discuss how future advances in identification of molecular alterations in NB may lead to more effective, less toxic therapies, and improve the prognosis for NB patients.

| S-EPMC3633592 | biostudies-literature

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