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.
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.
Project description:Gene expression profile at single cell level of 17 orthotopic-patient derived xenografts from neuroblastoma samples. All xenografts were obtained through the St. Jude Childhood Solid Tumor Network (https://cstn.stjude.cloud/)
Project description:Neuroblastoma is the most common extra cranial solid tumor derived from sympathoadrenal (SA) cells and characterized as either adrenergic or mesenchymal. Here, we compared four different protocols to differentiate induced pluripotent stem cells (iPSC) toward SA cells and intermediate cell states (neuromesodermal progenitors [NMP], trunk neural crest cells [tNCC]) as well as generating MYCN-driven tumors. Interestingly, the protocols that created cells with the highest level of NMP markers did not produce cells with the highest tNCC or SA cell markers. We identified a protocol that consistently produced cells with the highest level of SA markers using two iPSC lines of different genders. This protocol also generated tumors with the highest level of the neuroblastoma-specific marker, PHOX2B. Transcriptomally, however, each protocol generates tumors that resemble neuroblastoma. Two of the protocols repeatedly produced adrenergic neuroblastoma whereas the other two protocols were ambiguous. Thus, we identified a protocol that reliably generates adrenergic neuroblastoma.