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Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development

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Mau, King Hang Tommy, Karimlou, Donja, Barneda, David, Brochard, Vincent, Royer, Christophe, Leeke, Bryony, de Souza, Roshni A., Pailles, Mélanie, Percharde, Michelle, Srinivas, Shankar, Jouneau, Alice, Christian, Mark and Azuara, Véronique (2022) Dynamic enlargement and mobilization of lipid droplets in pluripotent cells coordinate morphogenesis during mouse peri-implantation development. Nature Communications, 13 (1). 3861. doi:10.1038/s41467-022-31323-2 ISSN 2041-1723.

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Official URL: https://doi.org/10.1038/s41467-022-31323-2

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QL Zoology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Lipids , Membrane lipids, Morphogenesis , Multipotent stem cells, Cell culture, Stem cells
Journal or Publication Title: Nature Communications
Publisher: Springer Science and Business Media LLC
ISSN: 2041-1723
Official Date: 5 July 2022
Dates:
DateEvent
5 July 2022Published
9 June 2022Accepted
Volume: 13
Number: 1
Article Number: 3861
DOI: 10.1038/s41467-022-31323-2
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 26 July 2022
Date of first compliant Open Access: 26 July 2022
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
P65250Genesis Research Trusthttp://dx.doi.org/10.13039/100012156
P54998Genesis Research Trusthttp://dx.doi.org/10.13039/100012156
BB/P005179/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/D52657X/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/P005209/2[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/H020233/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDImperial College Londonhttp://dx.doi.org/10.13039/501100000761
MC_UP_1605/4Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
MC_EX_MR/S015930/1UK Research and Innovationhttp://dx.doi.org/10.13039/100014013
MC_UP_1605/4UK Research and Innovationhttp://dx.doi.org/10.13039/100014013
MC_EX_MR/S015930/1Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
UNSPECIFIEDInstitut National de Recherche pour l'Agriculture, l'Alimentation et l'EnvironnementUNSPECIFIED
ANR-10- LABX73[ANR] Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
103788/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
UNSPECIFIEDAgroParisTechhttp://dx.doi.org/10.13039/501100005264
UNSPECIFIEDUniversity Of Oxfordhttp://dx.doi.org/10.13039/501100000769
UNSPECIFIEDUniversity of Warwickhttp://dx.doi.org/10.13039/501100000741
UNSPECIFIEDNottingham Trent Universityhttp://dx.doi.org/10.13039/100010016
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