Aradhana Sachdev, Kamaljot Gill, Maria Sckaff, Alisha M Birk, Olubankole Aladesuyi Arogundade, Katherine A Brown, Runvir S Chouhan, Patrick Oliver Issagholian-Lewin, Esha Patel, Hannah L Watry, Mylinh T Bernardi, Kathleen C Keough, Yu-Chih Tsai, Alec Simon Tulloch Smith, Bruce R Conklin, Claire Dudley Clelland
Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived induced pluripotent stem cell (iPSC) line and a non-diseased wild-type (WT) line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 frontotemporal dementia/amyotrophic lateral sclerosis in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes...
April 23, 2024: Proceedings of the National Academy of Sciences of the United States of America