Microglia Influence Neurofilament Deposition in ALS iPSC-Derived Motor Neurons

Genes

Reilly L. Allison¹  Allison D. Ebert¹  Jacob W. Adelman¹  Jenica Abrudan²  Michael T. Zimmermann²  Raul A. Urrutia²  Angela J. Mathison² 

[1] Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA;Genomic Science and Precision Medicine Center (GSPMC), Medical College of Wisconsin, Milwaukee, WI 53226, USA;

关键词: induced pluripotent stem cells;    amyotrophic lateral sclerosis;    astrocytes;    RNA sequencing;    cytokines;    anti-inflammatory;   

DOI  :  10.3390/genes13020241

来源: DOAJ

【 摘 要 】

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motor neuron loss is the primary phenotype, leading to muscle weakness and wasting, respiratory failure, and death. Although a portion of ALS cases are linked to one of over 50 unique genes, the vast majority of cases are sporadic in nature. However, the mechanisms underlying the motor neuron loss in either familial or sporadic ALS are not entirely clear. Here, we used induced pluripotent stem cells derived from a set of identical twin brothers discordant for ALS to assess the role of astrocytes and microglia on the expression and accumulation of neurofilament proteins in motor neurons. We found that motor neurons derived from the affected twin which exhibited increased transcript levels of all three neurofilament isoforms and increased expression of phosphorylated neurofilament puncta. We further found that treatment of the motor neurons with astrocyte-conditioned medium and microglial-conditioned medium significantly impacted neurofilament deposition. Together, these data suggest that glial-secreted factors can alter neurofilament pathology in ALS iPSC-derived motor neurons.

【 授权许可】

Unknown