Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell
Creators
- Kildisiute, G.1
- Kholosy, W.2
- Young, M.1
- Roberts, K.1
- Elmentaite, R.1
- R. van Hooff, S.2
- Pacyna, C.1
- Khabirova, E.1
- Piapi, A.3
- Thevanesan, C.3
- Bugallo-Blanco, E.3
- Burke, C.3
- Mamanova, L.1
- M. Keller, K.2
- Langenberg-Ververgaert, K.2
- Lijnzaad, P.2
- Margaritis, T.2
- Holstege, F.2
- L. Tas, M.2
- H.W.A. Wijnen, M.2
- M. van Noesel, M.2
- del Valle, I.3
- Barone, G.4
- van der Linden, R.5
- Duncan, C.5
- Anderson, J.5
- Achermann, J.3
- Haniffa, M.6
- Teichmann, S.1
- Rampling, D.4
- Sebire, N.4
- He, X.7
- R. de Krijger, R.8
- Barker, R.7
- Meyer, K.1
- Bayraktar, O.1
- Straathof, K.3
- Molenaar, J.2
- Behjati, S.9
- 1. Wellcome Sanger Institute, CB10 1SA Hinxton, UK
- 2. Princess Máxima Center for Pediatric Oncology
- 3. UCL Great Ormond Street Institute of Child Health
- 4. Great Ormond Street Hospital for Children (GOSH)
- 5. Hubrecht Institute
- 6. Institute of Cellular Medicine, Newcastle University
- 7. MRC-WT Cambridge Stem Cell Institute, University of Cambridge
- 8. Department of Pathology, University Medical Center Utrecht
- 9. Department of Paediatrics, University of Cambridge
Description
Neuroblastoma is a childhood cancer that resembles the developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues.
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