Global Transcriptomic analysis of Human iPSC-derived Neurons with IVS10+16 Tau Mutation
Cindy Tzu-Ling Huang1, Yonatan Cooper2, Yungui Zhou1, Giovanni Coppola2, Li Gan1,3 1Gladstone Institute of Neurological Disease, San Francisco, CA, USA; 2Departments of Psychiatry and Neurology, University of California, Los Angeles, CA, USA; 3Department of Neurology, University of California, San Francisco, CA, USA
MAPT is a gene that encodes the protein tau. Mutations in MAPT are well-known to cause frontotemporal dementia. However, how they lead to tauopathy in FTD remains elusive. Here, we focus on IVS10+16 (C to T) mutation (16th nucleotide of the intron after exon10), which causes alternative splicing to produce higher level of 4R tau. Using CRISPR gene-editing technique, we have successfully generated heterozygous and homozygous tau-mutated pluripotent stem cells (iPSCs) from wild-type (wt) tau iPSC. We validated that ratio of 4R/3R tau is elevated in mutant tau neurons compared to that of wt tau neurons. We next performed unbiased global gene analysis to uncover the genes and pathways that are altered in IVS10+16-tau neurons. Interestingly, several genes involved in synaptic vesicle and ribosome are significantly changed between wt and mutant neurons. We will further investigate the roles of these genes/pathways in IVS10+16 tau neurons.
Credits: None available.
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