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Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
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Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
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Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
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Paper
Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
2021
Overview
Abstract Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune cells contribute to disease progression. To better understand cellular heterogeneity in MB we use single-cell RNA sequencing, immunohistochemistry and deconvolution of transcriptomic data to profile neoplastic and immune populations in childhood MB samples. Neoplastic cells cluster primarily according to individual sample of origin which is in part due to the effect of chromosomal copy number gains and losses. Harmony alignment reveals novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes and are associated with clinical outcomes, including discrete photoreceptor-like cells in MB subgroups GP3 and GP4 and nodule-associated neuronally-differentiated cells in subgroup SHH. We definitively chart the spectrum of MB immune cell infiltrates, which include subgroup/subtype-associated developmentally-related neuron-pruning and antigen presenting myeloid cells. MB cellular diversity is recapitulated in genetically engineered mouse subgroup-specific models of MB. These findings provide a clearer understanding of both the neoplastic and immune cell heterogeneity in MB. Competing Interest Statement The authors have declared no competing interest. Footnotes * Conflict of Interests The authors have declared that no conflict of interest exists.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
