Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice
Abstract Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) hold promise for treating neurodegenerative and demyelinating disorders. However, comprehensive studies on their identity and safety remain limited. In this study, we demonstrate that hiPSC-NSCs adopt a ra...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53613-7 |
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| author | Marco Luciani Chiara Garsia Stefano Beretta Ingrid Cifola Clelia Peano Ivan Merelli Luca Petiti Annarita Miccio Vasco Meneghini Angela Gritti |
| author_facet | Marco Luciani Chiara Garsia Stefano Beretta Ingrid Cifola Clelia Peano Ivan Merelli Luca Petiti Annarita Miccio Vasco Meneghini Angela Gritti |
| author_sort | Marco Luciani |
| collection | DOAJ |
| description | Abstract Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) hold promise for treating neurodegenerative and demyelinating disorders. However, comprehensive studies on their identity and safety remain limited. In this study, we demonstrate that hiPSC-NSCs adopt a radial glia-associated signature, sharing key epigenetic and transcriptional characteristics with human fetal neural stem cells (hfNSCs) while exhibiting divergent profiles from glioblastoma stem cells. Long-term transplantation studies in mice showed robust and stable engraftment of hiPSC-NSCs, with predominant differentiation into glial cells and no evidence of tumor formation. Additionally, we identified the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) as a regulator of astroglial differentiation in hiPSC-NSCs. These findings provide valuable transcriptional and epigenetic reference datasets to prospectively define the maturation stage of NSCs derived from different hiPSC sources and demonstrate the long-term safety of hiPSC-NSCs, reinforcing their potential as a viable alternative to hfNSCs for clinical applications. |
| format | Article |
| id | doaj-art-8daf1e448b9c4dbdbc60072df517206a |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8daf1e448b9c4dbdbc60072df517206a2025-08-20T02:18:31ZengNature PortfolioNature Communications2041-17232024-11-0115112410.1038/s41467-024-53613-7Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in miceMarco Luciani0Chiara Garsia1Stefano Beretta2Ingrid Cifola3Clelia Peano4Ivan Merelli5Luca Petiti6Annarita Miccio7Vasco Meneghini8Angela Gritti9San Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteSan Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteSan Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteInstitute for Biomedical Technologies (ITB), National Research Council (CNR), via F.lli Cervi 93, 20054 SegrateInstitute of Genetics and Biomedical Research, UoS of Milan, National Research Council, RozzanoSan Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteInstitute for Biomedical Technologies (ITB), National Research Council (CNR), via F.lli Cervi 93, 20054 SegrateIMAGINE Institute, Université de Paris, Sorbonne Paris CitéSan Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteSan Raffaele Telethon Institute for Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific InstituteAbstract Human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NSCs) hold promise for treating neurodegenerative and demyelinating disorders. However, comprehensive studies on their identity and safety remain limited. In this study, we demonstrate that hiPSC-NSCs adopt a radial glia-associated signature, sharing key epigenetic and transcriptional characteristics with human fetal neural stem cells (hfNSCs) while exhibiting divergent profiles from glioblastoma stem cells. Long-term transplantation studies in mice showed robust and stable engraftment of hiPSC-NSCs, with predominant differentiation into glial cells and no evidence of tumor formation. Additionally, we identified the Sterol Regulatory Element Binding Transcription Factor 1 (SREBF1) as a regulator of astroglial differentiation in hiPSC-NSCs. These findings provide valuable transcriptional and epigenetic reference datasets to prospectively define the maturation stage of NSCs derived from different hiPSC sources and demonstrate the long-term safety of hiPSC-NSCs, reinforcing their potential as a viable alternative to hfNSCs for clinical applications.https://doi.org/10.1038/s41467-024-53613-7 |
| spellingShingle | Marco Luciani Chiara Garsia Stefano Beretta Ingrid Cifola Clelia Peano Ivan Merelli Luca Petiti Annarita Miccio Vasco Meneghini Angela Gritti Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice Nature Communications |
| title | Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice |
| title_full | Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice |
| title_fullStr | Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice |
| title_full_unstemmed | Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice |
| title_short | Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice |
| title_sort | human ipsc derived neural stem cells displaying radial glia signature exhibit long term safety in mice |
| url | https://doi.org/10.1038/s41467-024-53613-7 |
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