Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids
Abstract Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregul...
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| Format: | Article |
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Nature Portfolio
2025-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-08262-x |
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| author | R. Chris Estridge Z. Begum Yagci Dilara Sen Tyler J. Johnson Gautami R. Kelkar Travis S. Ptacek Jeremy M. Simon Albert J. Keung |
| author_facet | R. Chris Estridge Z. Begum Yagci Dilara Sen Tyler J. Johnson Gautami R. Kelkar Travis S. Ptacek Jeremy M. Simon Albert J. Keung |
| author_sort | R. Chris Estridge |
| collection | DOAJ |
| description | Abstract Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregulation. Human cerebral organoids might reveal these understudied aspects of UBE3A as they recapitulate diverse cell types of the developing human brain. In this study, scRNAseq on organoids reveals the effects of UBE3A disruption on cell type-specific compositions and transcriptomic alterations. In the absence of UBE3A, progenitor proliferation and structures are disrupted while organoid composition shifts away from proliferative cell types. We observe impacts on non-neuronal cells, including choroid plexus enrichment. Furthermore, EMX1+ cortical progenitors are negatively impacted; potentially disrupting corticogenesis and delaying excitatory neuron maturation. This work reveals impacts of UBE3A on understudied cell types and related neurodevelopmental processes and elucidates potential therapeutic targets. |
| format | Article |
| id | doaj-art-31e1ecf02c594903a66c9f6d501b3fac |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-31e1ecf02c594903a66c9f6d501b3fac2025-08-20T03:16:47ZengNature PortfolioCommunications Biology2399-36422025-05-018111910.1038/s42003-025-08262-xLoss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoidsR. Chris Estridge0Z. Begum Yagci1Dilara Sen2Tyler J. Johnson3Gautami R. Kelkar4Travis S. Ptacek5Jeremy M. Simon6Albert J. Keung7Department of Chemical and Biomolecular Engineering, North Carolina State UniversityDepartment of Chemical and Biomolecular Engineering, North Carolina State UniversityDepartment of Chemical and Biomolecular Engineering, North Carolina State UniversityDepartment of Chemical and Biomolecular Engineering, North Carolina State UniversityDepartment of Chemical and Biomolecular Engineering, North Carolina State UniversityUNC Neuroscience Center, The University of North Carolina at Chapel HillUNC Neuroscience Center, The University of North Carolina at Chapel HillDepartment of Chemical and Biomolecular Engineering, North Carolina State UniversityAbstract Angelman syndrome is a neurodevelopmental disorder caused by (epi)genetic lesions of maternal UBE3A. Research has focused largely on the role of UBE3A in neurons due to its imprinting in that cell type. Yet, evidence suggests there may be broader neurodevelopmental impacts of UBE3A dysregulation. Human cerebral organoids might reveal these understudied aspects of UBE3A as they recapitulate diverse cell types of the developing human brain. In this study, scRNAseq on organoids reveals the effects of UBE3A disruption on cell type-specific compositions and transcriptomic alterations. In the absence of UBE3A, progenitor proliferation and structures are disrupted while organoid composition shifts away from proliferative cell types. We observe impacts on non-neuronal cells, including choroid plexus enrichment. Furthermore, EMX1+ cortical progenitors are negatively impacted; potentially disrupting corticogenesis and delaying excitatory neuron maturation. This work reveals impacts of UBE3A on understudied cell types and related neurodevelopmental processes and elucidates potential therapeutic targets.https://doi.org/10.1038/s42003-025-08262-x |
| spellingShingle | R. Chris Estridge Z. Begum Yagci Dilara Sen Tyler J. Johnson Gautami R. Kelkar Travis S. Ptacek Jeremy M. Simon Albert J. Keung Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids Communications Biology |
| title | Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids |
| title_full | Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids |
| title_fullStr | Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids |
| title_full_unstemmed | Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids |
| title_short | Loss of UBE3A impacts both neuronal and non-neuronal cells in human cerebral organoids |
| title_sort | loss of ube3a impacts both neuronal and non neuronal cells in human cerebral organoids |
| url | https://doi.org/10.1038/s42003-025-08262-x |
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