Transcriptome analysis of neuroblastoma
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE96629 | GEO | 2017/03/15
SECONDARY ACCESSION(S): PRJNA379269
REPOSITORIES: GEO
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Project description:Neuroblastoma is the most common extracranial solid tumor and accounts for ~10% of pediatric cancer-related deaths. The exact cell-of-origin has yet to be elucidated, but it is generally accepted that neuroblastoma derives from the neural crest and should thus be considered an embryonal malignancy. About 50% of primary neuroblastoma tumors arise in the adrenal gland. Here we present an atlas of the developing mouse adrenal gland at a single cell level. Five main cell cluster groups (medulla, cortex, endothelial, stroma and immune) make up the mouse adrenal gland during fetal development. The medulla group, which is of neural crest origin, is further divided into seven clusters. Of interest is the Schwann cell precursor (SCP) and the neuroblast cluster, a highly cycling cluster that shares markers with sympathoblasts. The signature of the medullary SCP cluster differentiates neuroblastoma patients based on disease phenotype: the SCP signature score anti- correlates with ALK and MYCN expression, two indicators of poor prognosis. Furthermore, a high SCP signature score is associated with better overall survival rates. This study provides an insight in the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype.
2021-02-01 | GSE162238 | GEO
Project description:Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK. Expression profiling of murine neuroblastoma driven by MYCN were compared to those driven by mutated ALK and to mouse normal adrenal tissue.
2012-03-31 | E-GEOD-32386 | biostudies-arrayexpress
Project description:Ectoderm-derived neural crest is a transient structure arising during early embryogenesis in vertebrates. Neural crest consists of four derivatives based on their anterior- to posterior location along the body axis; cranial, vagal, trunk and sacral, respectively. We recently showed that trunk neural crest-specific gene MOXD1 functions as a tumor suppressor in trunk neural crest-derived childhood cancer form neuroblastoma and is essential for proper development of healthy adrenal glands. However, the role of MOXD1 during early embryogenesis is not known. Here, we conditionally knocked out MOXD1 in trunk neural crest cells before they become lineage-committed, using a CRISPR/Cas9 approach in chick embryos. Assessment of embryo growth showed that knockout of MOXD1 delayed development with knockout embryos being smaller. RNA sequencing of trunk-derived neural crest cells from control and knockout embryos showed enrichment of genes connected to gland development, copper ion metabolism and neuroblastoma progression. In conclusion, MOXD1 is important during early and prolonged embryonic development with effects on gland formation, possibly mediated via its role in copper metabolism.
2023-09-13 | GSE242700 | GEO
Project description:Neuroblastoma is a childhood cancer believed to result from dysfunctional development. Its origin during embryogenesis remains poorly understood. The lack of appropriate models has hindered in-depth mapping of early tumor-driving events. Here, we identify a novel tumor suppressor gene associating with worse outcome in MOXD1-deprived high-risk patients, by applying bulk and single cell RNA sequencing data of neuroblastoma and human fetal adrenal glands. Trunk neural crest-specific MOXD1 discriminates cell populations during normal and tumor development, with implications for deciphering neuroblastoma cell origin. We created an embryonic conditional knockout model and show that cell type-specific loss of MOXD1 leads to disrupted organ homeostasis and failed adrenal gland formation, home for neuroblastoma. We show that MOXD1 is a tumor suppressor gene in zebrafish, chick, and mice in vivo models.
2023-09-06 | GSE242157 | GEO
Project description:Transcriptome analysis of healthy adrenal glands, mbryonic neural crest cells, and neuroblastoma
| PRJNA379263 | ENA
Project description:Multimodality treatment of high-risk neuroblastoma can be effective, but up to 50% of children experience recurrent disease with fatal outcome. Extensive genetic intratumoral heterogeneity and diverse clinical outcomes pose therapeutic challenges in treating children affected by this aggressive disease. Several hypotheses have been proposed to explain the heterogeneity of neuroblastoma, including a possible origin from multipotent neural crest stem cells (NCSCs). Utilizing an in vivo mouse genetics approach, we demonstrate that lineage-restricted sympathoadrenal (SA) progenitors and not NCSCs are the cellular origin of neuroblastoma. Human neuroblastoma tissue is composed of two spatially juxtaposed cell types, neuroblasts and Schwann cells, both cell types derive from neural crest (NC) lineage. This composition mimics the architecture of sympathetic ganglions (SG) as well as of adrenal medulla at the late stage of neural crest (NC) development. Similarly to SG, SOX10 is restricted to Schwannian cells and is not present in tumorigenic neuroblasts. Transcriptional landscape of Sox genes can serve as paradigmatic model for stage identification along NC lineage development. While early multipotent NCSCs are characterized by the expression of Sox9/Sox10 transcription factors (TF), committed SA progenitor identity is defined by the presence of Sox4/Sox11 TFs. Molecularly, we show that the core transcriptional network that orchestrate neuroblastoma maintenance is highly reminiscent of the SA progenitors. Taken together, the data presented here show that neuroblastoma cells functionally resemble the committed SA progenitors, while lacking specific stem cell program.
2020-01-01 | GSE133014 | GEO
Project description:High-risk 11q deleted neuroblastomas (NBs) typically display an undifferentiated/poorly differentiated morphology. NB is thought to develop from Schwann cell precursors (SCPs) and un-differentiated neural crest derived cells (NCC). It is therefore vital to understand the mechanisms involved in the block of differentiation. We showed that an important and novel role for oncogenic ALK-ERK1/2-SP1 signaling may be the maintenance of an undifferentiated state of transformed NC-derived progenitors that is achieved by repression of DLG2, a tumor suppressor in NB. DLG2 is expressed in the ‘bridge signature’ that represents the transcriptional transition state when neural crest cells or Schwann Cell Precursors (SCP) become chromaffin cells of the adrenal gland. The importance of SP1 and DLG2 in this process is highlighted by our findings that restoring DLG2 expression spontaneously drives NB differentiation. Further, genetic analysis of high-risk 11q deletion NB patient identified genetic lesions in the DLG2 gene, Our data also suggest that further exploration of other ‘bridge genes’ may help to better understand the mechanisms underlying the differentiation of NC-derived progenitors and their contribution to NB.
2020-11-25 | PXD017946 | Pride
Project description:This GEO series contains human scRNA-seq data of Neuroblastoma patients, used in two manuscripts. n=7 paired samples, primary tumour vs. bone marrow metastases n=2 non-paired samples, bone marrow metastases Titles: Article 1 PUBLISHED: Neuroblastoma plasticity during metastatic progression stems from the dynamics of an early sympathetic transcriptomic trajectory See Citation and PubMed ID below. Article 2 UNDER REVIEW: Single-cell analyses of paired primary neuroblastoma tumor and bone marrow metastases reveals intra-patient heterogeneity and therapy-resistant subpopulations Abstract of article 1: Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases of NB plasticity and heterogeneity remains incomplete. They may be rooted in developmental trajectories of their lineage of origin, the sympatho-adrenal neural crest. We found that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterized transcriptome states of NB cells and their dynamics over time and space, and compared them to those of fetal sympatho-adrenal tissues and patient tumors and bone marrow samples. Here we report remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian and patient datasets, we identified a list of genes upregulated upon bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach. Despite being key pathological features, Neuroblastoma (NB) plasticity and Heterogeneity remain largely misunderstood. They may be rooted in complex developmental trajectories of their embryonic lineage of origin, the sympatho-adrenal neural crest. We found that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterized transcriptional states of NB cells and their dynamics over time and space, and compared them to those of fetal sympatho-adrenal tissues and patient tumors, including matched primary tumor and bone marrow samples. We found remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian model and patient datasets, we identified a list of candidate genes upon bone marrow involvement associated with NB growth dependency, validating the relevance of our multimodal approach.
2024-09-13 | GSE245175 | GEO
Project description:Neuroblastoma is an embryonal tumor arising from the neural crest. It can be mimicked in mice by neural crest-specific overepxression of oncogenes such as MYCN or mutated ALK.
2012-04-01 | GSE32386 | GEO
Project description:Despite their indisputable importance in neuroblastoma (NB) pathology, knowledge of the bases of NB plasticity and heterogeneity remains incomplete. They may be rooted in developmental trajectories of their lineage of origin, the sympatho-adrenal neural crest. We found that implanting human NB cells in the neural crest of the avian embryo allows recapitulating the metastatic sequence until bone marrow involvement. Using deep single cell RNA sequencing, we characterized transcriptome states of NB cells and their dynamics over time and space, and compared them to those of fetal sympatho-adrenal tissues and patient tumors and bone marrow samples. Here we report remarkable transcriptomic proximities restricted to an early sympathetic neuroblast branch that co-exist with phenotypical adaptations over disease progression and recapitulate intratumor and interpatient heterogeneity. Combining avian and patient datasets, we identified a list of genes upregulated upon bone marrow involvement and associated with growth dependency, validating the relevance of our multimodal approach.
2024-09-13 | GSE237881 | GEO