Institute of Reproductive and Developmental Biology, Department of Metabolism, Digestion, and Reproduction, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Physiology and Metabolism Laboratory, The Francis Crick Institute, London, NW1 1AT, UK.
Nat Commun. 2022 Jul 5;13(1):3861. doi: 10.1038/s41467-022-31323-2.
Mammalian pre-implantation embryos accumulate substantial lipids, which are stored in lipid droplets (LDs). Despite the fundamental roles of lipids in many cellular functions, the significance of building-up LDs for the developing embryo remains unclear. Here we report that the accumulation and mobilization of LDs upon implantation are causal in the morphogenesis of the pluripotent epiblast and generation of the pro-amniotic cavity in mouse embryos, a critical step for all subsequent development. We show that the CIDEA protein, found abundantly in adipocytes, enhances lipid storage in blastocysts and pluripotent stem cells by promoting LD enlargement through fusion. The LD-stored lipids are mobilized into lysosomes at the onset of lumenogenesis, but without CIDEA are prematurely degraded by cytosolic lipases. Loss of lipid storage or inactivation of lipophagy leads to the aberrant formation of multiple cavities within disorganised epithelial structures. Thus, our study reveals an unexpected role for LDs in orchestrating tissue remodelling and uncovers underappreciated facets of lipid metabolism in peri-implantation development.
哺乳动物的着床前胚胎积累了大量的脂质，这些脂质储存在脂滴（LDs）中。尽管脂质在许多细胞功能中起着重要作用，但对于发育中的胚胎来说，积累和动员 LD 对于其发育的意义仍不清楚。在这里，我们报告说，在着床时 LD 的积累和动员对于多能滋养外胚层的形态发生和小鼠胚胎原尿囊腔的产生是因果关系的，这是所有后续发育的关键步骤。我们发现，CIDEA 蛋白在脂肪细胞中大量存在，通过促进 LD 通过融合而扩大来增强囊胚和多能干细胞中的脂质储存。在囊胚发生开始时，LD 储存的脂质被动员到溶酶体中，但如果没有 CIDEA，脂质会被细胞质脂酶过早降解。脂质储存的丧失或噬脂作用的失活会导致上皮结构紊乱中多个腔的异常形成。因此，我们的研究揭示了 LD 在协调组织重塑中的意外作用，并揭示了着床前发育中脂质代谢的被低估的方面。
