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Using human pluripotent stem cells to study post-transcriptional mechanisms of neurodegenerative diseases.

TitleUsing human pluripotent stem cells to study post-transcriptional mechanisms of neurodegenerative diseases.
Publication TypeJournal Article
Year of Publication2012
AuthorsPatani R, Sibley CR, Chandran S, Ule J
JournalBrain Res
Date Published2012 Jun 26
KeywordsAnimals, Disease Models, Animal, Humans, Models, Biological, Neurodegenerative Diseases, Pluripotent Stem Cells, Protein Processing, Post-Translational, RNA, RNA-Binding Proteins, Species Specificity, Stem Cells

Post-transcriptional regulation plays a major role in the generation of cell type diversity. In particular, alternative splicing increases diversification of transcriptome between tissues, in different cell types within a tissue, and even in different compartments of the same cell. The complexity of alternative splicing has increased during evolution. With increasing sophistication, however, comes greater potential for malfunction of these intricate processes. Indeed, recent years have uncovered a wealth of disease-causing mutations affecting RNA-binding proteins and non-coding regions on RNAs, highlighting the importance of studying disease mechanisms that act at the level of RNA processing. For instance, mutations in TARDBP and FUS, or a repeat expansion in the intronic region of the C9ORF72 gene, can all cause amyotrophic lateral sclerosis. We discuss how interspecies differences highlight the necessity for human model systems to complement existing non-human approaches to study neurodegenerative disorders. We conclude by discussing the improvements that could further increase the promise of human pluripotent stem for cell-based disease modeling. This article is part of a Special Issue entitled "RNA-Binding Proteins".

Alternate JournalBrain Res.
PubMed ID22285437
Grant List089701 / / Wellcome Trust / United Kingdom
MC_U105185858 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom
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