Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development.
Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development.
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DOI：
10.1038/s41467-022-31323-2
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发表时间：
2022-07-05
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
哺乳动物植入前的胚胎积累了大量的脂类，这些脂类储存在脂滴(LD)中。尽管脂质在许多细胞功能中起着基础性的作用，但构建LDS对发育中的胚胎的意义仍不清楚。在此，我们报道了在小鼠胚胎中，LDS的积累和动员是多能外胚层的形态发生和前羊膜腔形成的原因，这是所有后续发育的关键步骤。我们发现，在脂肪细胞中大量存在的CIDEA蛋白，通过融合促进LD扩大，增强了囊胚和多能干细胞中的脂肪储存。LD储存的脂类在管腔形成开始时被动员到溶酶体中，但没有CIDEA的情况下，胞液脂肪酶会过早地降解。脂类储存的丧失或脂噬功能的失活会导致在组织紊乱的上皮结构中异常形成多个空洞。因此，我们的研究揭示了LDS在协调组织重塑方面的意想不到的作用，并揭示了在植入围生期发育中被低估的脂代谢方面。在植入子宫之前，哺乳动物胚胎储存了大量的脂肪。在这里，作者揭示了多能干细胞的脂肪储存和形态发生在围着床期发育过程中是如何从根本上联系起来的。
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. Prior to its implantation into the uterus, the mammalian embryo stores substantial lipids. Here the authors unveil how lipid storage and morphogenesis of pluripotent stem cells are fundamentally connected during peri-implantation development.
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影响因子：
11.8
作者：
Amadei G;Lau KYC;De Jonghe J;Gantner CW;Sozen B;Chan C;Zhu M;Kyprianou C;Hollfelder F;Zernicka-Goetz M
通讯作者：
Zernicka-Goetz M
影响因子：
64.8
作者：
Chan, Chii Jou;Costanzo, Maria;Hiiragi, Takashi
通讯作者：
Hiiragi, Takashi
影响因子：
4.8
作者：
Brasaemle, DL;Rubin, B;Londos, C
通讯作者：
Londos, C
DOI：
10.1073/pnas.2018362118
发表时间：
2021-03-09
影响因子：
11.1
作者：
Arena R;Bisogno S;Gąsior Ł;Rudnicka J;Bernhardt L;Haaf T;Zacchini F;Bochenek M;Fic K;Bik E;Barańska M;Bodzoń-Kułakowska A;Suder P;Depciuch J;Gurgul A;Polański Z;Ptak GE
通讯作者：
Ptak GE
影响因子：
7.7
作者：
Barneda D;Planas-Iglesias J;Gaspar ML;Mohammadyani D;Prasannan S;Dormann D;Han GS;Jesch SA;Carman GM;Kagan V;Parker MG;Ktistakis NT;Klein-Seetharaman J;Dixon AM;Henry SA;Christian M
通讯作者：
Christian M