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Single cell RNA seq of the developing murine adrenal gland reveals correlation of Schwann cell precursor signature to neuroblastoma phenotype.

ABSTRACT: Single cell RNA seq of the developing murine adrenal gland reveals correlation of Schwann cell precursor signature to neuroblastoma phenotype.

PROVIDER: PRJNA681184 | ENA |

REPOSITORIES: ENA

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Single cell RNA seq of the developing murine adrenal gland reveals correlation of Schwann cell precursor signature to neuroblastoma phenotype.

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.

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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 anticorrelates 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 into the developing adrenal gland and introduces the SCP gene signature as being of interest for further research in understanding neuroblastoma phenotype.

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