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Remodeled single-cell landscape in the metastatic bone marrow in human neuroblastoma unraveled by multi-omics and deep multiplex imaging

ABSTRACT: Remodeled single-cell landscape in the metastatic bone marrow in human neuroblastoma unraveled by multi-omics and deep multiplex imaging

PROVIDER: PRJNA722308 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14250941.fastq.gz	Fastqsanger.gz
	SRR14250942.fastq.gz	Fastqsanger.gz
	SRR14250943.fastq.gz	Fastqsanger.gz
	SRR14250944.fastq.gz	Fastqsanger.gz
	SRR14250945.fastq.gz	Fastqsanger.gz

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Remodeled single-cell landscape in the metastatic bone marrow in human neuroblastoma unraveled by multi-omics and deep multiplex imaging

Project description:Single-cell assessment of bone marrow metastases is essential to decipher the entire spectrum of tumor heterogeneity in solid cancers with bone marrow involvement. We used multi-epitope-ligand cartography (MELC) to spatially profile 20 biomarkers in 35,000 disseminated tumor cells (DTCs), hematopoietic and mesenchymal cells from eight neuroblastoma bone marrow metastases. We developed DeepFLEX, a single-cell image analysis pipeline for MELC data that combines deep learning-based cell and nucleus segmentation and overcomes frequent challenges of multiplex imaging methods. Comparisons of cell type proportions between samples indicated that microenvironmental changes in the bone marrow are associated with tumor cell infiltration and therapy response. Hierarchical clustering of DTCs revealed multiple phenotypes with highly diverse expression of markers such as FAIM2, which we propose as a complementary marker to capture DTC heterogeneity in neuroblastoma. This single-cell atlas is an important step towards a deeper understanding of DTCs and their interactions with the bone marrow niche.

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Landscape of Bone Marrow Metastasis in Human Neuroblastoma Unraveled by Transcriptomics and Deep Multiplex Imaging.

Project description:While the bone marrow attracts tumor cells in many solid cancers leading to poor outcome in affected patients, comprehensive analyses of bone marrow metastases have not been performed on a single-cell level. We here set out to capture tumor heterogeneity and unravel microenvironmental changes in neuroblastoma, a solid cancer with bone marrow involvement. To this end, we employed a multi-omics data mining approach to define a multiplex imaging panel and developed DeepFLEX, a pipeline for subsequent multiplex image analysis, whereby we constructed a single-cell atlas of over 35,000 disseminated tumor cells (DTCs) and cells of their microenvironment in the metastatic bone marrow niche. Further, we independently profiled the transcriptome of a cohort of 38 patients with and without bone marrow metastasis. Our results revealed vast diversity among DTCs and suggest that FAIM2 can act as a complementary marker to capture DTC heterogeneity. Importantly, we demonstrate that malignant bone marrow infiltration is associated with an inflammatory response and at the same time the presence of immuno-suppressive cell types, most prominently an immature neutrophil/granulocytic myeloid-derived suppressor-like cell type. The presented findings indicate that metastatic tumor cells shape the bone marrow microenvironment, warranting deeper investigations of spatio-temporal dynamics at the single-cell level and their clinical relevance.

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