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

Published: 17 April 2025| Version 1 | DOI: 10.17632/3wg6kztvvd.1
Contributors:
, Stefano Beretta, Ingrid Cifola, vasco meneghini, Angela Gritti

Description

The dataset includes the raw data of graphs shown in figures 1, 2, 3, 5, 6, and 7 and in supplementary figures 1, 2, 3, 4, 5, 7, and 8 of the paper: Human iPSC-derived neural stem cells displaying radial glia signature exhibit long-term safety in mice. Luciani M, Garsia C, Beretta S, Cifola I, Peano C, Merelli I, Petiti L, Miccio A, Meneghini V, Gritti A. Nat Commun. 2024 Nov 1;15(1):9433. doi: 10.1038/s41467-024-53613-7. PMID: 39487141 The bulk RNA-seq, SREBF1-deficient RNA-seq, and ChIP-seq data generated in this study have been deposited at GEO under accession number GSE239446. The single-cell RNA-seq data generated in this study have been deposited at GEO under accession number GSE238206. The processed RNA-seq, ChIP-seq, and scRNA-seq data (list of DEGs and GO terms) are available in Supplementary Data 1-4 files. 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.

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Institutions

Ospedale San Raffaele, Universita Vita Salute San Raffaele

Categories

Induced Pluripotent Stem Cell, Transcriptomics, Epigenetics, Neural Stem Cell, Single-Cell RNA Sequencing

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