In a study published online July 18 in Nature Neuroscience, researchers report important findings toward characterizing and improving induced pluripotent stem cell (iPSC) models of ALS. By comparing the transcriptomes of iPSC-derived spinal motor neurons (MNs), fetal and adult spinal tissues, and spinal MNs extracted from control and ALS patients postmortem samples, the researchers found that the gene expression signatures of iPSC-derived MNs resembled fetal tissue more than adult MNs. They further characterized gene networks that are active in different stages of maturation and aging of spinal MNs, and showed that ALS leads to dysregulation of these networks. The findings suggest that activation of key maturation and aging pathways in iPSC-derived MN models of ALS could produce cellular models that more closely mimic human ALS.
Ho R, Sances S, Gowing G, Amoroso MW, O’Rourke JG, Sahabian A, Wichterle H, Baloh RH, Sareen D, Svendsen CN. ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks. Nat Neurosci. 2016 Jul 18. [Pubmed].