Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice

Marco Luciani, Chiara Garsia, Stefano Beretta, Ingrid Cifola, Clelia Peano, Ivan Merelli, Luca Petiti, Annarita Miccio, Vasco Meneghini () and Angela Gritti ()
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Marco Luciani: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute
Chiara Garsia: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute
Stefano Beretta: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute
Ingrid Cifola: 20054 Segrate
Clelia Peano: Rozzano
Ivan Merelli: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute
Luca Petiti: 20054 Segrate
Annarita Miccio: Sorbonne Paris Cité
Vasco Meneghini: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute
Angela Gritti: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute

Nature Communications, 2024, vol. 15, issue 1, 1-24

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-53613-7

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