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Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of brain tumors

ABSTRACT: Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of brain tumors

PROVIDER: PRJNA835744 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19122800_1.fastq.gz	Fastqsanger.gz
	SRR19122800_2.fastq.gz	Fastqsanger.gz
	SRR19122801_1.fastq.gz	Fastqsanger.gz
	SRR19122801_2.fastq.gz	Fastqsanger.gz
	SRR19122802_1.fastq.gz	Fastqsanger.gz

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Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of brain tumors

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Project description:Cell state evolution underlies tumor development and response to therapy1, but mechanisms specifying cancer cell states and intratumor heterogeneity are incompletely understood. Schwannomas are the most common tumors of the peripheral nervous system and are treated with surgery and ionizing radiation2–5. Schwannomas can oscillate in size for many years after radiotherapy6,7, suggesting treatment may reprogram schwannoma cells or the tumor microenvironment. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas. We find schwannomas are comprised of 2 molecular groups distinguished by reactivation of neural crest development pathways or misactivation of nerve injury mechanisms that specify cancer cell states and the architecture of the tumor immune microenvironment. Schwannoma molecular groups can arise independently, but ionizing radiation is sufficient for epigenetic reprogramming of neural crest to immune-enriched schwannoma by remodeling chromatin accessibility, gene expression, and metabolism to drive schwannoma cell state evolution and immune cell infiltration. To define functional genomic mechanisms underlying epigenetic reprograming of schwannomas, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of cancer evolution and establish a paradigm of epigenetic reprograming of cancer in response to radiotherapy.

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Single-cell RNA sequencing reveals cellular and molecular reprograming landscape of gliomas and lung cancer brain metastases.

Project description:BackgroundBrain malignancies encompass gliomas and brain metastases originating from extracranial tumours including lung cancer. Approximately 50% of patients with lung adenocarcinoma (LUAD) will eventually develop brain metastases. However, the specific characteristics of gliomas and lung-to-brain metastases (LC) are largely unknown.MethodsWe applied single-cell RNA sequencing to profile immune and nonimmune cells in 4 glioma and 10 LC samples.ResultsOur analysis revealed that tumour microenvironment (TME) cells are present in heterogeneous subpopulations. LC reprogramed cells into immune suppressed state, including microglia, macrophages, endothelial cells, and CD8+ T cells, with unique cell proportions and gene signatures. Particularly, we identified that a subset of macrophages was associated with poor prognosis. ROS (reactive oxygen species)-producing neutrophils was found to participant in angiogenesis. Furthermore, endothelial cells participated in active communication with fibroblasts. Metastatic epithelial cells exhibited high heterogeneity in chromosomal instability (CIN) and cell population.ConclusionsOur findings provide a comprehensive understanding of the heterogenicity of the tumor microenvironment and tumour cells and it will be crucial for successful immunotherapy development for brain metastasis of lung cancer.

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