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Chunk #40 — CAVEATS AND LIMITATIONS OF hiPSC MODELS

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Genetics of Alcohol Use Disorder: A Role for Induced Pluripotent Stem Cells?
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While hiPSC models offer a promising approach to studying AUD, there are several limitations worth noting. First, one would ideally study neurons at a mature stage comparable to neurons in adults. However, hiPSC-derived neurons are immature and lack some of the complex connectivity of adult neurons. Recently, transcriptional profiling of neurons and astrocytes derived from hiPSCs indicated these cells most closely resemble fetal cells (Brennand et al. 2015; TCW et al. 2017). Optimization of components in the differentiation culture medium has helped promote the presence of more synaptically mature neurons (Bardy et al., 2015). Second, while it is advantageous to focus on one cell type, the interactions with other cell types play an important role in development and functionality.