Integrated single-nucleus and spatial transcriptomics define tumour cell metaprograms and tumour microenvironment organisation in choroid plexus tumours.

Stress- and hypoxia-associated dedifferentiation programs are selectively enriched in paediatric B choroid plexus tumours and correlate with poorer survival.

• Why it matters: CPT biology is hard to reconcile across histology and methylation subgroups, and risk stratification lacks subtype-specific molecular and microenvironmental mechanisms.
• What they did: Single-nucleus RNA sequencing of 43 CPTs was integrated with 12 non-neoplastic choroid plexus references, and spatial transcriptomics was applied to 16 tumour sections plus 2 normal samples.
• The result: Tumour programs cluster by methylation subtype rather than WHO grade, with pedB showing enriched interferon, hypoxia, early stress, and TGF-β signalling, spatially linked to pro-angiogenic myeloid populations.

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