Single-cell MultiOmics and spatial transcriptomics demonstrate neuroblastoma developmental plasticity.
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Xu Y, Lou D, Chen P, Li G, Usoskin D, Pan J, Li F, Huang S, Hess C, Tang R, Hu X, Yu J, Arceo M, de Krijger RR, Tischler AS, Schlisio S, Ernfors P, Hu Y, Wang J
Dev. Cell - (-) - [2025-05-06; online 2025-05-06]
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.
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 40347947
DOI 10.1016/j.devcel.2025.04.013
Crossref 10.1016/j.devcel.2025.04.013
pii: S1534-5807(25)00251-5