Fig. 1

Establishing hiPSC-derived neuronal models for studying selective vulnerability to Tau pathology. a Schematic depicting hiPSC differentiation to distinct neuronal subtypes along with their identifying marker gene expression. Created with BioRender.com. b PCA of DIV21 96 target gene expression data from 5 hiPSC-neuron subtypes across 5 hiPSC donor lines. The proportion of variance for PC1 is 20.73%, while the proportion of variance for PC2 is 17.04%. c Heat map with hierarchical clustering depicts select marker gene expression at DIV21 in 5 hiPSC-neuron subtypes across 5 hiPSC donor lines. Log10 normalized expression values are scaled per neuronal population to indicate highly expressed genes. CI = cortical inhibitory hiPSC-neurons, CE = cortical excitatory hiPSC-neurons, Hypo = hypothalamic hiPSC-neurons, mDA = midbrain dopaminergic hiPSC-neurons, SC = spinal cord hiPSC-neurons. d Immunofluorescence of DIV21 hiPSC-neurons differentiated to 5 distinct neuronal subtypes. Scale bar = 50 µm. e Quantification of DIV21 hiPSC-neuron percent of nuclei positive for cortical layer (CTIP2, TBR1) and regional identity markers (FOXG1, FOXA2, and HOXB4). F Western blot analysis of total Tau (TauC, red) and actin (green) from DIV16 hiPSC-neurons differentiated to 5 neuronal subtypes. L = ladder, labeled with molecular weight (kDa)