Centre of Reproduction, Development and Aging, Faculty of Health Sciences, University of Macau, Macau, China.
Bioimaging and Stem Cell Core Facility, Faculty of Health Sciences, University of Macau, Macau, China.
Cell Rep. 2021 Nov 30;37(9):110063. doi: 10.1016/j.celrep.2021.110063.
Pluripotent stem cells (PSCs) can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements can relieve the dependence on de novo lipogenesis and shift global metabolism. However, it is largely unexplored how specific lipid components regulate metabolism and subsequently the pluripotency state. In this study, we report that the metabolic landscape of human PSCs (hPSCs) is shifted by signaling lipid lysophosphatidic acid (LPA), which naturally exists. LPA leads to a distinctive transcriptome profile that is not associated with de novo lipogenesis. Although exogenous lipids such as cholesterol, common free fatty acids, and LPA can affect cellular metabolism, they are not necessary for maintaining primed pluripotency. Instead, LPA induces distinct and reversible phenotypes in cell cycle, morphology, and mitochondria. This study reveals a distinct primed state that could be used to alter cell physiology in hPSCs for basic research and stem cell applications.
多能干细胞（PSCs）可以在具有不同特征的细胞状态连续体中维持。外源性脂质补充可以减轻对从头脂生成的依赖，并改变整体代谢。然而，特定脂质成分如何调节代谢，进而调节多能状态，在很大程度上仍未得到探索。在这项研究中，我们报告说，信号脂质溶血磷脂酸（LPA）会改变人 PSCs（hPSCs）的代谢景观，LPA 天然存在。LPA 导致独特的转录组谱，与从头脂生成无关。尽管胆固醇、常见游离脂肪酸和 LPA 等外源性脂质可以影响细胞代谢，但它们对于维持初始多能性并非必需。相反，LPA 在细胞周期、形态和线粒体中诱导出独特且可逆的表型。这项研究揭示了一种独特的初始状态，可用于改变 hPSCs 的细胞生理学，用于基础研究和干细胞应用。
