ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis

Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-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 ofAbhd11hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast,Abhd11overexpression exerted anti-apoptotic effects in ESCs. Moreover,Abhd11knockout disturbed GSK3 beta/beta-Catenin and ERK signaling transduction. Finally,Abhd11knockout 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胚胎干细胞（ESC）的维持至关重要这一观点。最近，含α/β水解酶结构域（ABHD）的蛋白质已成为脂质合成或降解过程中新型的关键调节因子，然而它们在胚胎干细胞中的功能尚未得到研究。在本研究中，我们通过经典的功能缺失和获得实验揭示了ABHD11在胚胎干细胞功能中的作用。Abhd11基因敲除阻碍了胚胎干细胞的扩增和分化，引发自噬流和细胞凋亡。相反，Abhd11过表达在胚胎干细胞中发挥抗凋亡作用。此外，Abhd11基因敲除干扰了GSK3β/β - 连环蛋白和ERK信号转导。最后，Abhd11基因敲除导致与脂质合成、糖酵解和氨基酸代谢相关的关键代谢酶表达异常，并且ABHD11有助于脂质代谢的内稳态。这些发现为ABHD蛋白质的广泛作用提供了新的见解，并强调了脂质代谢调节因子在干细胞功能控制中的重要性。