Neoplastic and immune single-cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma
| Autor: | Daniel S Malawsky, Martin Sill, Bridget Sanford, Andrew M. Donson, Siddhartha Mitra, Sujatha Venkataraman, Seth J. Weir, Kent Riemondy, Nicholas Willard, Andrea Griesinger, Rajeev Vibhakar, Timothy R. Gershon, Todd C. Hankinson, Robert J. Wechsler-Reya, Jay R. Hesselberth, Alexandra Garancher, Anandani Nellan, Jennifer Ocasio, Nicholas K. Foreman, Vladimir Amani, Michael H. Handler |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Disease Biology Transcriptome 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Biomarkers Tumor Humans Cerebellar Neoplasms Medulloblastoma RNA medicine.disease 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Basic and Translational Investigations Cancer research Immunohistochemistry Neurology (clinical) |
| Zdroj: | Neuro Oncol |
| Popis: | Background Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune cells contribute to disease progression. We aimed to determine the influence of neoplastic and immune cell diversity on MB biology in patient samples and animal models. Methods To better characterize cellular heterogeneity in MB we used single-cell RNA sequencing, immunohistochemistry, and deconvolution of transcriptomic data to profile neoplastic and immune populations in patient samples and animal models across childhood MB subgroups. Results Neoplastic cells cluster primarily according to individual sample of origin which is influenced by chromosomal copy number variance. Harmony alignment reveals novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes, including photoreceptor and glutamatergic neuron-like cells in molecular subgroups GP3 and GP4, and a specific nodule-associated neuronally differentiated subpopulation in the sonic hedgehog subgroup. We definitively chart the spectrum of MB immune cell infiltrates, which include subpopulations that recapitulate developmentally related neuron-pruning and antigen-presenting myeloid cells. MB cellular diversity matching human samples is mirrored in subgroup-specific mouse models of MB. Conclusions These findings provide a clearer understanding of the diverse neoplastic and immune cell subpopulations that constitute the MB microenvironment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|