83: Dup15q in Focus: Single-cell traces of metabolic and synaptic change

Perez Y et al., Nature Communications - This episode reviews a single-cell and spatial transcriptomic study of dup15q syndrome using patient postmortem cortex and hiPSC-derived cortical organoids. The work maps developmental metabolic shifts, layer-identity changes, and postnatal synaptic transcriptional burdens linked to autism. Key terms: dup15q, single-cell RNA-seq, cortical organoids, glycolysis, autism. Study Highlights:The authors profiled 345,861 postmortem nuclei and 106,302 organoid cells to map cell-type specific transcriptional changes in dup15q. Early organoid progenitors and deep-layer neurons showed increased glycolysis, degraded layer identity, and reduced neurite arborization. In adolescent-adult postmortem cortex, upper-layer neurons carried elevated synaptic transcriptional burden that overlaps idiopathic autism. Conserved gene co-expression modules link metabolic reprogramming to synaptic and ion-channel networks across organoids and tissue. Conclusion:Dup15q drives dynamic, cell-type specific molecular shifts from prenatal metabolic reprogramming in progenitors and deep-layer neurons to postnatal synaptic transcriptional changes in upper-layer neurons, highlighting metabolic and synaptic networks as convergent features of syndromic and idiopathic autism. Music:Enjoy the music based on this article at the end of the episode. Article title:Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism First author:Perez Y Journal:Nature Communications DOI:10.1038/s41467-025-61184-4 Reference:Perez Y, Velmeshev D, Wang L, et al. Single-cell analysis of dup15q syndrome reveals developmental and postnatal molecular changes in autism. Nature Communications. 2025;16:6177. doi:10.1038/s41467-025-61184-4 License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/ Support:Base by Base – Stripe donations: https://donate.stripe.com/7sY4gz71B2sN3RWac5gEg00 Official website https://basebybase.com On PaperCast Base by Base you'll discover the latest in genomics, functional genomics, structural genomics, and proteomics. Episode link: https://basebybase.com/episodes/dup15q-single-cell-changes-autism-ep83 QC:This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-07-22. QC Scope:- article metadata and core scientific claims from the narration- excludes analogies, intro/outro, and music- transcript coverage: Audited the main scientific narrative described in the transcript against the canonical article. QC Summary:- factual score: 10/10- metadata score: 10/10- supported core claims: 6- claims flagged for review: 0- metadata checks passed: 4- metadata issues found: 0 Metadata Audited:- article_doi- article_title- article_journal- license Factual Items Audited:- dup15q leads to increased glycolysis in deep-layer neurons during fetal-stage organoids- DL neurons show degraded layer identity with co-expression of DL and UL markers- Sholl analysis shows reduced arborization of dup15q deep-layer neurons in organoids and after xenotransplantation into mice- adolescent/adult postmortem UL neurons exhibit increased synaptic transcriptional burden overlapping idiopathic autism- MAPK signaling pathways are implicated and converge with idiopathic ASD- Conserved co-expression modules between organoids and postmortem tissue (L5_6.2 glycolysis; L5_6.7 synaptic/ion-channel) QC result: Pass.