April 2022 - Polina Kameneva

Dr. Polina Kameneva

MedUni Wien RESEARCHER OF THE MONTH April 2022

Neuroblastoma is the most common solid extra-cranial tumor in children, with an enigmatic origin that precludes the development of relapse-free treatments. These tumors often form in the adrenal gland region and are composed of sympathetic neuronal precursors staled in their development. We focused on unravelling the development of cells building the adrenal gland with a single-cell transcriptomic approach to reveal the secret of neuroblastoma. We found a large human-specific population of sympathetic neuronal precursors which reside inside the adrenal medulla. Moreover, we proved that these sympathetic precursors unlike other sympathetic neurons in human originate from nerve-associated multipotent glial cells and their intermediate developmental states correspond to malignant cells from neuroblastoma. Altogether, we found the potential cellular source of neuroblastoma with a unique embryonic developmental pathway, which can be targeted during treatment.

Selected Literature

1. Johnsen, J.I., Dyberg, C. & Wickström, M. Neuroblastoma—A Neural Crest Derived Embryonal Malignancy. Frontiers in Molecular Neuroscience 12 (2019).
2. Boeva, V. et al. Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries. Nat Genet 49, 1408-1413 (2017).
3. van Groningen, T. et al. Neuroblastoma is composed of two super-enhancer-associated differentiation states. Nat Genet 49, 1261-1266 (2017).
4. Furlan, A. et al. Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla. Science 357 (2017).
5. Kastriti, M.E. et al. Schwann Cell Precursors Generate the Majority of Chromaffin Cells in Zuckerkandl Organ and Some Sympathetic Neurons in Paraganglia. Frontiers in Molecular Neuroscience 12 (2019).
6. Kameneva, P. et al. Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin. Nature Genetics (2021).
7. Kameneva, P. et al. Evolutionary switch in expression of key markers between mouse and human leads to mis-assignment of cell types in developing adrenal medulla. Cancer Cell 39, 590-591 (2021).