Single-cell MultiOmics and spatial transcriptomics demonstrate neuroblastoma developmental plasticity
Neuroblastoma, the most prevalent extracranial pediatric solid tumor, arises from neural crest progeny cells. It exhibits substantial developmental plasticity and intratumoral heterogeneity, leading to survival rates below 50% in high-risk cases. The regulatory mechanisms underlying this plasticity remain largely elusive. In this integrative study, we used single-cell MultiOmics from a mouse spontaneous tumor model and spatial transcriptomics from human patient samples to dissect the transcriptional and epigenetic landscapes that govern developmental states in neuroblastoma. We identified developmental intermediate states in high-risk neuroblastomas critical for malignant transitions and uncovered extensive epigenetic priming with latent capacity for diverse state transitions. Furthermore, we mapped enhancer gene regulatory networks (eGRNs) and tumor microenvironments sustaining these aggressive states. State transitions and malignancy could be interfered with by targeting transcription factors controlling the eGRNs.
Authors
- Patrik Ernfors (ORCID: https://orcid.org/0000-0002-1140-3986)
- Arthur S. Tischler (ORCID: https://orcid.org/0000-0002-9726-5739)
- Dmitry Usoskin (ORCID: https://orcid.org/0000-0001-9122-6387)
- Maria Arceo
- Ronald R. de Krijger (ORCID: https://orcid.org/0000-0001-6871-1296)
- Yunyun Xu (ORCID: https://orcid.org/0000-0002-6371-054X)
- Ping Chen (ORCID: https://orcid.org/0000-0002-8068-1891)
- Corine J. Hess (ORCID: https://orcid.org/0000-0001-8517-8948)
- Daohua Lou (ORCID: https://orcid.org/0000-0001-7031-998X)
- Ruze Tang
- Shungen Huang (ORCID: https://orcid.org/0000-0002-1978-3143)
- Jian Pan (ORCID: https://orcid.org/0000-0002-6845-8486)
- Yizhou Hu (ORCID: https://orcid.org/0000-0002-2635-0258)
- Susanne Schlisio (ORCID: https://orcid.org/0000-0002-2605-3771)
- Jian Wang (ORCID: https://orcid.org/0000-0003-4949-4753)
- Fang Li (ORCID: https://orcid.org/0000-0003-3629-4779)
- Gang Li (ORCID: https://orcid.org/0000-0001-9585-1382)
- Juanjuan Yu
- Xiaohan Hu (ORCID: https://orcid.org/0000-0001-5040-6023)
Institutions
- Tufts Medical Center (US)
- Karolinska Institutet (SE)
- Soochow University (CN)
- Integrated Cardio Metabolic Centre (SE)
- Princess Máxima Center (NL)
- Children's Hospital of Suzhou University (CN)
- First Affiliated Hospital of Soochow University (CN)
Publication Details
- Journal
- Developmental Cell
- Published
- 2025-05-09
- DOI
- https://doi.org/10.1016/j.devcel.2025.04.013
- Citations
- 10
- Primary Topic
- Neuroblastoma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 13.89
Funders
- Åke Wiberg Stiftelse
- Suzhou Municipal Health Commission
- National Natural Science Foundation of China
- Cancerfonden
- Svenska Sällskapet för Medicinsk Forskning
- Karolinska Institutet
- Knut och Alice Wallenbergs Stiftelse
- Natural Science Foundation of Jiangsu Province
- Jiangsu Science and Technology Department
- Science and Technology Program of Suzhou