Salome Funes, Jonathan Jung, Del Hayden Gadd, Michelle Mosqueda, Jianjun Zhong, Shankaracharya, Matthew Unger, Karly Stallworth, Debra Cameron, Melissa S Rotunno, Pepper Dawes, Megan Fowler-Magaw, Pamela J Keagle, Justin A McDonough, Sivakumar Boopathy, Miguel Sena-Esteves, Jeffrey A Nickerson, Cathleen Lutz, William C Skarnes, Elaine T Lim, Dorothy P Schafer, Francesca Massi, John E Landers, Daryl A Bosco
Microglia play a pivotal role in neurodegenerative disease pathogenesis, but the mechanisms underlying microglia dysfunction and toxicity remain to be elucidated. To investigate the effect of neurodegenerative disease-linked genes on the intrinsic properties of microglia, we studied microglia-like cells derived from human induced pluripotent stem cells (iPSCs), termed iMGs, harboring mutations in profilin-1 (PFN1) that are causative for amyotrophic lateral sclerosis (ALS). ALS-PFN1 iMGs exhibited evidence of lipid dysmetabolism, autophagy dysregulation and deficient phagocytosis, a canonical microglia function...
March 20, 2024: Nature Communications