Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy

PLoS One. 2014 Jul 23;9(7):e103112. doi: 10.1371/journal.pone.0103112. eCollection 2014.

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / analysis
  • Calcium / metabolism
  • Cell Line
  • Cell Survival
  • Coculture Techniques
  • Humans
  • Motor Neurons / pathology*
  • Muscular Atrophy, Spinal / pathology*
  • Muscular Atrophy, Spinal / physiopathology
  • Neurogenesis
  • Sensory Receptor Cells / pathology*
  • Stem Cells / pathology*

Substances

  • Calcium

Grants and funding

Support was provided by a New Faculty Pilot Research Award (#3305943) funded by the Research Affairs Committee at the Medical College of Wisconsin. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.