Mangiameli et al., Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.
Description
The dataset includes the row data of graphs shown in figures 1-6 of the paper: Mangiameli E, Cecchele A, Morena F, Sanvito F, Matafora V, Cattaneo A, Della Volpe L, Gnani D, Paulis M, Susani L, Martino S, Di Micco R, Bachi A, Gritti A. Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes. Stem Cell Reports. 2021 Jun 8;16(6):1478-1495. doi: 10.1016/j.stemcr.2021.04.011. Epub 2021 May 13. PubMed PMID: 33989519; PubMed Central PMCID: PMC8190599. The lipidomic dataset reported in the paper (Figure 7) is available at MetaboLights, accession number MTBLS1501 (https://www.ebi.ac.uk/metabolights/MTBLS1501). Globoid cell leukodystrophy (GLD) is a rare neurodegenerative lysosomal storage disease caused by an inherited deficiency of β-galactocerebrosidase (GALC). GLD pathogenesis and therapeutic correction have been poorly studied in patient neural cells. Here, we investigated the impact of GALC deficiency and lentiviral vector-mediated GALC rescue/overexpression in induced pluripotent stem cell (iPSC)-derived neural progenitors and neuronal/glial progeny obtained from two GLD patients. GLD neural progeny displayed progressive psychosine storage, oligodendroglial and neuronal defects, unbalanced lipid composition, and early activation of cellular senescence, depending on the disease-causing mutation. The partial rescue of the neural differentiation program upon GALC reconstitution and psychosine clearance suggests multiple mechanisms contributing to neural pathology in GLD. Also, the pathological phenotype associated to supraphysiological GALC levels highlights the need of regulated GALC expression for proper human neural commitment/differentiation. These data have important implications for establishing safe therapeutic strategies to enhance disease correction of GLD.