Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, α/β-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3β/β-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function.

越来越多的证据支持脂质代谢对于维持胚胎干细胞（ESC）至关重要的观点。近来，含α/β-水解酶结构域（ABHD）的蛋白质已成为脂质合成或降解中的新型关键调节剂，但尚未研究其在ESC中的功能。在这项研究中，我们使用经典的功能丧失和获得实验揭示了ABHD11在ESC功能中的作用。淘汰赛Abhd11阻碍了ESC的扩增和分化，触发了自噬通量和细胞凋亡。相反，Abhd11过表达在ESC中发挥抗凋亡作用。此外，Abhd11基因敲除干扰了GSK3β/β-Catenin和ERK信号转导。最后，Abhd11敲除导致与脂质合成，糖酵解和氨基酸代谢有关的关键代谢酶的错误表达，而ABHD11促进了脂质代谢的稳态。这些发现为ABHD蛋白的广泛作用提供了新的见解，并突出了脂质代谢调节剂在干细胞功能控制中的重要性。