RRC ID 61687
著者 Ogawa Y, Tanaka M, Tanabe M, Suzuki T, Togawa T, Fukushige T, Kanekura T, Sakuraba H, Oishi K.
タイトル Impaired neural differentiation of induced pluripotent stem cells generated from a mouse model of Sandhoff disease.
ジャーナル PLoS One
Abstract Sandhoff disease (SD) is a glycosphingolipid storage disease that arises from mutations in the Hexb gene and the resultant deficiency in β-hexosaminidase activity. This deficiency results in aberrant lysosomal accumulation of the ganglioside GM2 and related glycolipids, and progressive deterioration of the central nervous system. Dysfunctional glycolipid storage causes severe neurodegeneration through a poorly understood pathogenic mechanism. Induced pluripotent stem cell (iPSC) technology offers new opportunities for both elucidation of the pathogenesis of diseases and the development of stem cell-based therapies. Here, we report the generation of disease-specific iPSCs from a mouse model of SD. These mouse model-derived iPSCs (SD-iPSCs) exhibited pluripotent stem cell properties and significant accumulation of GM2 ganglioside. In lineage-directed differentiation studies using the stromal cell-derived inducing activity method, SD-iPSCs showed an impaired ability to differentiate into early stage neural precursors. Moreover, fewer neurons differentiated from neural precursors in SD-iPSCs than in the case of the wild type. Recovery of the Hexb gene in SD-iPSCs improved this impairment of neuronal differentiation. These results provide new insights as to understanding the complex pathogenic mechanisms of SD.
巻・号 8(1)
ページ e55856
公開日 2013-1-1
DOI 10.1371/journal.pone.0055856
PII PONE-D-12-17545
PMID 23383290
PMC PMC3561340
MeSH Animals Cell Differentiation* / genetics Disease Models, Animal Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / ultrastructure Male Mice Mice, Knockout Neurons / cytology* Neurons / metabolism Neurons / ultrastructure Phenotype Sandhoff Disease / etiology* Sandhoff Disease / genetics beta-Hexosaminidase beta Chain / genetics beta-Hexosaminidase beta Chain / metabolism
IF 2.74
リソース情報
ヒト・動物細胞 iPS-MEF-Ng-20D-17(APS0001) EB3(AES0139) MC3T3-G2/PA6(RCB1127)