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

Rickie Patani, Christopher R Sibley, Siddharthan Chandran, Jernej Ule*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)129-138
Number of pages10
JournalBrain Research
Volume1462
DOIs
Publication statusPublished - 26 Jun 2012

Keywords

  • REPERFUSION INJURY
  • HEXANUCLEOTIDE REPEAT
  • MYOTONIC-DYSTROPHY
  • EFFICIENT NEURAL CONVERSION
  • Neurodegenerative disease
  • DIRECTED DIFFERENTIATION
  • FUNCTIONAL ORGANIZATION
  • Pluripotent stem cell (hPSC)
  • SPINAL MUSCULAR-ATROPHY
  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • HUMAN IPS CELLS
  • CORTICOSPINAL TRACT
  • RNA-binding protein (RBP)
  • Induced pluripotent stem cell (iPSC)
  • Embryonic stem cell (ESC)

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