Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components
Abstract Extracellular vesicles (EVs) play a critical role in the development of neural cells in the central nervous system (CNS). Human neural rosettes (hNRs) are radial cell structures that assemble from induced pluripotent stem cells (hiPSCs) and recapitulate some stages of neural tube morphogene...
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Nature Portfolio
2025-01-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-86094-9 |
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| author | Malena Herrera Lopez Matías Bertone Arolfo Mónica Remedi Laura Gastaldi Carlos Wilson Gonzalo G. Guendulain Danilo Ceschin Andrés Cardozo Gizzi Alfredo Cáceres Ana Lis Moyano |
| author_facet | Malena Herrera Lopez Matías Bertone Arolfo Mónica Remedi Laura Gastaldi Carlos Wilson Gonzalo G. Guendulain Danilo Ceschin Andrés Cardozo Gizzi Alfredo Cáceres Ana Lis Moyano |
| author_sort | Malena Herrera Lopez |
| collection | DOAJ |
| description | Abstract Extracellular vesicles (EVs) play a critical role in the development of neural cells in the central nervous system (CNS). Human neural rosettes (hNRs) are radial cell structures that assemble from induced pluripotent stem cells (hiPSCs) and recapitulate some stages of neural tube morphogenesis. Here we show that hiPSCs and hNRs secrete EVs (hiPSC-EVs and hNR-EVs) with distinctive protein cargoes. Remarkably, hNR-EVs carry neuronal and glial cellular components involved in human CNS development. Importantly, hNR-EVs stimulate stem cells to change their cellular morphology and promote neurite growth in human and murine neurons with a significant dysregulation of SOX2 levels. This transcription factor modulates both neural differentiation and pluripotency. Interestingly, these effects were inhibited by antibodies against an unexpected neuroglial cargo of hNR-EVs: the major proteolipid protein (PLP). These findings show that hNRs secrete bioactive EVs containing neural components and might contribute as trophic factors during human neurodevelopment. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-cb13f7c825004a938570a6048f9dfe802025-01-19T12:20:34ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-86094-9Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular componentsMalena Herrera Lopez0Matías Bertone Arolfo1Mónica Remedi2Laura Gastaldi3Carlos Wilson4Gonzalo G. Guendulain5Danilo Ceschin6Andrés Cardozo Gizzi7Alfredo Cáceres8Ana Lis Moyano9Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Centro de Investigación en Medicina Traslacional “Severo R. Amuchástegui” (CIMETSA), Instituto Universitario de Ciencias Biomédicas de Córdoba (IUCBC), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Abstract Extracellular vesicles (EVs) play a critical role in the development of neural cells in the central nervous system (CNS). Human neural rosettes (hNRs) are radial cell structures that assemble from induced pluripotent stem cells (hiPSCs) and recapitulate some stages of neural tube morphogenesis. Here we show that hiPSCs and hNRs secrete EVs (hiPSC-EVs and hNR-EVs) with distinctive protein cargoes. Remarkably, hNR-EVs carry neuronal and glial cellular components involved in human CNS development. Importantly, hNR-EVs stimulate stem cells to change their cellular morphology and promote neurite growth in human and murine neurons with a significant dysregulation of SOX2 levels. This transcription factor modulates both neural differentiation and pluripotency. Interestingly, these effects were inhibited by antibodies against an unexpected neuroglial cargo of hNR-EVs: the major proteolipid protein (PLP). These findings show that hNRs secrete bioactive EVs containing neural components and might contribute as trophic factors during human neurodevelopment.https://doi.org/10.1038/s41598-025-86094-9CNSNeurodevelopmentExtracellular vesiclesStem cellsNeurite outgrowthSOX2 |
| spellingShingle | Malena Herrera Lopez Matías Bertone Arolfo Mónica Remedi Laura Gastaldi Carlos Wilson Gonzalo G. Guendulain Danilo Ceschin Andrés Cardozo Gizzi Alfredo Cáceres Ana Lis Moyano Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components Scientific Reports CNS Neurodevelopment Extracellular vesicles Stem cells Neurite outgrowth SOX2 |
| title | Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| title_full | Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| title_fullStr | Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| title_full_unstemmed | Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| title_short | Human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| title_sort | human neural rosettes secrete bioactive extracellular vesicles enriched in neuronal and glial cellular components |
| topic | CNS Neurodevelopment Extracellular vesicles Stem cells Neurite outgrowth SOX2 |
| url | https://doi.org/10.1038/s41598-025-86094-9 |
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