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Single-cell transcriptomics of neuroblastoma tumors

ABSTRACT: Single-cell transcriptomics of neuroblastoma tumors

PROVIDER: PRJNA1067585 | ENA |

REPOSITORIES: ENA

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Single-cell transcriptomics of neuroblastoma tumors

Project description:Neuroblastoma is a rare embryonic tumor arising from neural crest development and is responsible for 15% of pediatric cancer-related deaths. Over the past years, several single-cell transcriptome studies were performed to investigate the cell-of-origin and tumor heterogeneity. These individual studies typically involved a limited number of neuroblastoma tumors. To overcome this limitation, we integrated seven single-cell or single-nucleus data sets into a harmonized cell atlas covering 362,991 cells across 68 patient samples. We use this integrated atlas to decipher the transcriptional tumoral landscape of neuroblastoma at single-cell resolution. Notably, within the tumor compartment, we find associations between transcriptomic profiles and clinical outcomes. In addition, we characterize the complex immune cell landscape of neuroblastoma and uncover considerable heterogeneity amongst tumor-associated macrophages. Finally, we showcase the utility of our atlas as a resource by expanding it with new data and using it as a reference for data-driven cell type prediction.

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Dissecting the cellular architecture of neuroblastoma bone marrow metastasis using single-cell transcriptomics and epigenomics

Project description:The bone marrow (BM) is the third most frequent site of metastasis for solid tumors, creating an unfavorable clinical outcome. It provides a unique microenvironment that promotes growth of tumors, however, the role of different BM cells, their molecular features, and their interactions with tumor cells, are poorly defined. Here, we investigate the BM niche in neuroblastoma (NB), a pediatric cancer of the sympathetic nervous system. NB has been molecularly defined at the primary cancer site, yet, the metastatic site is poorly characterized. We performed single-cell transcriptomics (scRNA-seq) and epigenomic profiling (scATAC-seq) of BM aspirates from 11 subjects spanning three major NB subtypes: patients with MYCN amplification (MNA), ATRX mutations (ATRXmut), and cases that lack these alterations (sporadic): NB cases were then compared to five age-matched and metastasis-free BM (controls), followed by in-depth single cell analyses of tissue diversity and cell-cell interactions. We present the first map of the epigenetic and transcriptomic effects of bone marrow metastases. Our analyses demonstrate that tumor cells in the metastatic niche display plasticity that differs among NB subtypes. NB cells via cell-cell interaction signal to the bone marrow microenvironment, rewiring specifically monocytes, which exhibit M1 and M2 features, marked by activation of pro- and anti-inflammatory programs, and express tumor-promoting factors, reminiscent of tumor-associated macrophages. Our study may provide the basis for a therapeutic approach, targeting tumor-to-microenvironment interactions.

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Project description:Gene expression profile at single cell level of neuroblastoma tumors

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Gene expression profile at single cell level of neuroblastoma tumors and their tumor microenvironment

Project description:Neuroblastoma (NBL) tumors are considered heterogeneous tumors. So far, little detailed information available on their immune environment. We used single cell RNA sequencing (scRNA-seq) to analyze the tumor microenvironment of neuroblastoma.

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Gene expression profile at single cell level of neuroblastoma tumors and their tumor microenvironment

Project description:Gene expression profile at single cell level of neuroblastoma tumors and their tumor microenvironment