期刊
STEM CELL REPORTS
卷 12, 期 6, 页码 1329-1341出版社
CELL PRESS
DOI: 10.1016/j.stemcr.2019.04.009
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资金
- Swedish Research Council [2011-2651, 2016-02112]
- EU Joint Programme for Neurodegenerative Disease (JPND) [529-2014-7500]
- Ragnar Soderbergs stiftelse [M245/11]
- Ahlen-stiftelsen [mA9/h11, mA5/h12, mB8/h13, mB8/h14, mA1/h15, mA1/h16]
- Hjarnfonden [FO2018-0027]
- Ulla-Carin Lindquists stiftelse for ALS forskning
- Petrus och Augusta Hedlunds Stiftelse [M-2018-0876]
- Swedish Society for Medical Research (SSMF)
- Lundbeck Foundation
- SSMF
- Early Postdoc Mobility fellowship from the Swiss National Science Foundation [172233]
- Novo Nordisk Foundation Laureate Program
- Novo Nordisk Fonden [NNF15OC0016016] Funding Source: researchfish
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.
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