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

Gaoke Liu; Yan Ruan; Junlei Zhang; Xueyue Wang; Wei Wu; Ping He; Jiali Wang; Jiaxiang Xiong; Yuda Cheng; Lianlian Liu; Yi Yang; Yanping Tian; Rui Jian

doi:10.3389/fcell.2020.00570

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

Front Cell Dev Biol. 2020 Jul 7:8:570. doi: 10.3389/fcell.2020.00570. eCollection 2020.

Authors

Gaoke Liu¹, Yan Ruan¹, Junlei Zhang¹, Xueyue Wang¹, Wei Wu², Ping He³, Jiali Wang¹, Jiaxiang Xiong⁴, Yuda Cheng¹, Lianlian Liu¹, Yi Yang⁴, Yanping Tian¹, Rui Jian¹

Affiliations

¹ Laboratory of Stem Cell and Developmental Biology, Department of Histology and Embryology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.
² Department of Thoracic Surgery, Southwest Hospital, First Affiliated Hospital Third Military Medical University, Chongqing, China.
³ Cardiac Surgery Department, Southwest Hospital, First Affiliated Hospital Third Military Medical University, Chongqing, China.
⁴ Experimental Center of Basic Medicine, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China.

Abstract

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.

Keywords: ABHD11; embryonic stem cell; knockout; overexpression; self-renewal.