Modeling ALS with motor neurons derived from human induced pluripotent stem cells

Samuel Sances, Lucie I. Bruijn, Siddharthan Chandran, Kevin Eggan, Ritchie Ho, Joseph R. Klim, Matthew Livesey, Emily Lowry, Jeffrey D. Macklis, David Rushton, Cameron Sadegh, Dhruv Sareen, Hynek Wichterle, Su-Chun Zhang, Clive N. Svendsen*

*Corresponding author for this work

Research output: Contribution to journalLiterature reviewpeer-review

Abstract

Directing the differentiation of induced pluripotent stem cells into motor neurons has allowed investigators to develop new models of amyotrophic lateral sclerosis (ALS). However, techniques vary between laboratories and the cells do not appear to mature into fully functional adult motor neurons. Here we discuss common developmental principles of both lower and upper motor neuron development that have led to specific derivation techniques. We then suggest how these motor neurons may be matured further either through direct expression or administration of specific factors or coculture approaches with other tissues. Ultimately, through a greater understanding of motor neuron biology, it will be possible to establish more reliable models of ALS. These in turn will have a greater chance of validating new drugs that may be effective for the disease.

Original languageEnglish
Pages (from-to)542-553
Number of pages12
JournalNature Neuroscience
Volume19
Issue number4
Early online date29 Mar 2016
DOIs
Publication statusE-pub ahead of print - 29 Mar 2016

Keywords

  • AMYOTROPHIC-LATERAL-SCLEROSIS
  • NEURAL PROGENITOR CELLS
  • CEREBRAL-CORTEX
  • DIRECTED DIFFERENTIATION
  • PROJECTION NEURONS
  • SPINAL-CORD
  • IN-VIVO
  • MUTANT SOD1
  • MOUSE MODEL
  • CORTICAL HYPEREXCITABILITY

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