Mangiameli et al., Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes.

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.

该数据集包含了论文中图1至6所示的图表的行数据：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. 基于人类 iPSC 的球状细胞白质营养不良神经发育模型揭示患者和细胞类型特异性疾病表型。干细胞报告。2021年6月8日；16(6)：1478-1495. doi: 10.1016/j.stemcr.2021.04.011. Epub 2021年5月13日。PubMed PMID: 33989519；PubMed Central PMCID: PMC8190599。

论文中报告的脂质组学数据集（图7）可在 MetaboLights 上获得，访问号为 MTBLS1501（https://www.ebi.ac.uk/metabolights/MTBLS1501）。

球状细胞白质营养不良（GLD）是一种由β-半乳糖脑苷脂酶（GALC）遗传性缺乏引起的罕见神经退行性溶酶体储存疾病。GLD 的发病机制和治疗方法在患者神经细胞中的研究尚显不足。在本研究中，我们探讨了 GALC 缺陷和慢病毒载体介导的 GALC 救援/过表达对来自两名 GLD 患者的诱导多能干细胞（iPSC）来源的神经祖细胞和神经元/胶质祖细胞的 影响。GLD 神经祖细胞表现出心理辛的逐渐积累、少突胶质细胞和神经元缺陷、脂质组成失衡以及早期细胞衰老，这些现象取决于疾病致因突变。GALC 重构和心理辛清除后神经分化程序的局部救援表明，GLD 神经病理可能由多种机制共同作用。此外，与超生理水平的 GALC 相关的病理表型突出了对 GALC 表达进行调控以实现人类神经定向/分化的必要性。这些数据对于建立安全的治疗策略以增强 GLD 疾病校正具有重要意义。