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Chunk #13 — RESULTS — Transcriptomic profile differences of high-PRS and low-PRS microglial cells in response to ethanol exposure

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Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.
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We next determined the effects of intermittent ethanol exposure on the transcriptomic profiles of the iPSC-derived microglia (n = 9, four high-PRS and five low-PRS; table S1). Exposure to ethanol did not affect human microglial cell identity, as determined by comparing our microglial bulk RNA-seq data with the publicly available single-cell RNA-seq dataset of adult human brain cells (fig. S4A) (45). Some ADH and ALDH genes—including ADH5, ALDH1A1, ALDH1A2, and ALDH2—which encode enzymes involved in metabolizing ethanol into acetaldehyde and acetate (51), were found to be expressed by human microglia (table S2), suggesting that they may metabolize ethanol.