Modeling Motor Neuron Resilience in ALS Using Stem Cells.

IF: 7.294

Cited by: 24

Abstract

Oculomotor neurons, which regulate eye movement, are resilient to degeneration in the lethal motor neuron disease amyotrophic lateral sclerosis (ALS). It would be highly advantageous if motor neuron resilience could be modeled in vitro. Toward this goal, we generated a high proportion of oculomotor neurons from mouse embryonic stem cells through temporal overexpression of PHOX2A in neuronal progenitors. We demonstrate, using electrophysiology, immunocytochemistry, and RNA sequencing, that in vitro-generated neurons are bona fide oculomotor neurons based on their cellular properties and similarity to their in vivo counterpart in rodent and man. We also show that in vitro-generated oculomotor neurons display a robust activation of survival-promoting Akt signaling and are more resilient to the ALS-like toxicity of kainic acid than spinal motor neurons. Thus, we can generate bona fide oculomotor neurons in vitro that display a resilience similar to that seen in vivo.

Keywords

Gene Expression

LCM-seq

ALS

LCM sequencing

Onuf’s nucleus

Phox2a

RNA sequencing

amyotrophic lateral sclerosis

neuronal vulnerability and resistance

oculomotor neurons

spinal motor neurons

stem cells

MeSH terms

Amyotrophic Lateral Sclerosis

Animals

Cell Differentiation

Cell Survival

Homeodomain Proteins

Humans

Mice

Motor Neurons

Mouse Embryonic Stem Cells

Proto-Oncogene Proteins c-akt

Signal Transduction

Authors

Allodi, Ilary

Nijssen, Jik

Benitez, Julio Aguila

Schweingruber, Christoph

Fuchs, Andrea

Bonvicini, Gillian

Cao, Ming

Kiehn, Ole

Hedlund, Eva

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