Researchers may be one step closer to recreating motor neurons from people with ALS according to a new study led by Washington University School of Medicine’s Andrew Yoo in St. Louis, Missouri.
The strategy, which involves the transfection of microRNAs miR-9 and miR-124, and the transcription factors ISL1 and LHX3, enables adult human fibroblasts to be directly reprogrammed into human spinal cord motor neurons. What’s more, most of the cells generated by this method appeared to be functional, firing multiple action potentials when depolarized.
The strategy is one of a growing number of techniques that aims to streamline the production of human motor neurons in the laboratory to investigate their role in neurodegenerative diseases including ALS (see Son et al., 2011). The approach is based on previous studies from Yoo, while in Gerald Crabtree’s laboratory at Stanford University School of Medicine in California, which found that human fibroblasts exposed to miR-9 and miR-124 became neurons in culture (Yoo et al., 2011).
The study is published on September 7 in Cell Stem Cell.
The strategy may be a potentially key alternative to existing indirect reprogramming methods because the cells might retain epigenetic marks which may contribute to ALS (Mertens et al., 2015; Huh et al., 2016; Ho et al., 2016).
Now, Yoo’s team is using this approach to investigate how motor neurons may be impacted by the aging process. The results may provide insight into how these changes may contribute to late-onset neurodegenerative diseases including ALS. Stay tuned.
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