Induced pluripotent stem cell lines from Huntington's disease mice undergo neuronal differentiation while showing alterations in the lysosomal pathway

Neurobiology of Disease

Elena Cattaneo¹  Marco Onorati²  Valentina Castiglioni²  Christelle Rochon² 

[1] Corresponding author. Fax: [phone].;Department of Pharmacological Sciences and Centre for Stem Cell Research, Università degli Studi di Milano, Via Balzaretti 9-20133 Milano, Italy;

关键词: Induced pluripotent stem cells;    Huntington's disease;    Neuronal differentiation;    R6/2;   

DOI  :  

来源: DOAJ

【 摘 要 】

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an excessive expansion of a CAG trinucleotide repeat in the gene encoding the protein huntingtin, resulting in an elongated stretch of glutamines near the N-terminus of the protein. Here we report the derivation of a collection of 11 induced pluripotent stem (iPS) cell lines generated through somatic reprogramming of fibroblasts obtained from the R6/2 transgenic HD mouse line. We show that CAG expansion has no effect on reprogramming efficiency, cell proliferation rate, brain-derived neurotrophic factor level, or neurogenic potential. However, genes involved in the cholesterol biosynthesis pathway, which is altered in HD, are also affected in HD-iPS cell lines. Furthermore, we found a lysosomal gene upregulation and an increase in lysosome number in HD-iPS cell lines. These observations suggest that iPS cells from HD mice replicate some but not all of the molecular phenotypes typically observed in the disease; additionally, they do not manifest increased cell death propensity either under self-renewal or differentiated conditions. More studies will be necessary to transform a revolutionary technology into a powerful platform for drug screening approaches.

【 授权许可】

Unknown