Celeste Parra Bravo, Alice Maria Giani, Jesus Madero Perez, Zeping Zhao, Yuansong Wan, Avi J Samelson, Man Ying Wong, Alessandro Evangelisti, Ethan Cordes, Li Fan, Pearly Ye, Daphne Zhu, Tatyana Pozner, Maria Mercedes, Tark Patel, Allan Yarahmady, Gillian K Carling, Fredrik H Sterky, Virginia M Y Lee, Edward B Lee, Michael DeTure, Dennis W Dickson, Manu Sharma, Sue-Ann Mok, Wenjie Luo, Mingrui Zhao, Martin Kampmann, Shiaoching Gong, Li Gan
Tauopathies are age-associated neurodegenerative diseases whose mechanistic underpinnings remain elusive, partially due to a lack of appropriate human models. Here, we engineered human induced pluripotent stem cell (hiPSC)-derived neuronal lines to express 4R Tau and 4R Tau carrying the P301S MAPT mutation when differentiated into neurons. 4R-P301S neurons display progressive Tau inclusions upon seeding with Tau fibrils and recapitulate features of tauopathy phenotypes including shared transcriptomic signatures, autophagic body accumulation, and reduced neuronal activity...
March 28, 2024: Cell