脂肪肝病（NAFLD）早期阶段的脂肪变性会在没有干预的情况下发展成非酒精性脂肪性肝炎（NASH）和肝功能衰竭。尽管已经开发出动物模型，但仍缺乏与人类相关的脂肪变性建模和药物和靶点发现平台。《自然生物技术》杂志上的Hendriks等人报道，在人类胎肝器官样品上引入营养和遗传触发器，利用人类胎肝器官样本重新呈现脂肪变性。利用这些经过工程改造的肝脏器官样本衍生的脂肪变性模型，筛选出可缓解脂肪变性的药物，并挖掘有效化合物的共同机制。另外，受到药物筛选结果的启发，对35个脂质代谢基因进行了CRISPR-LOF筛选，并确定FADS2是脂肪变性的关键调节因子。©2023. 作者（们）。

Steatosis, as the early stage of nonalcoholic fatty acid disease (NAFLD), would progress into nonalcoholic steatohepatitis (NASH) and liver failure without intervention. Despite the development of animal models, there is still a lack of the human-relevant platform for steatosis modeling and drug & target discovery. Hendriks et al., reporting in Nature Biotechnology, leveraged human fetal liver organoids to recapitulate steatosis by introducing nutritional and genetic triggers. Using these engineered liver organoid-derived steatosis models, they screened drugs that alleviate steatosis, and mined common mechanism of effective compounds. Further, inspired by the results of drug screening, the arrayed CRISPR-LOF screening targeting 35 lipid metabolism genes was performed, and FADS2 was identified as a critical regulator of steatosis.© 2023. The Author(s).