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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
05 07 2022
Historique:
received: 08 04 2021
accepted: 09 06 2022
entrez: 5 7 2022
pubmed: 6 7 2022
medline: 8 7 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35790717
doi: 10.1038/s41467-022-31323-2
pii: 10.1038/s41467-022-31323-2
pmc: PMC9256688
doi:

Substances chimiques

Lipids 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3861

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P005179/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/H020233/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/P005209/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 103788/Z/14/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1605/4
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_EX_MR/S015930/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/D52657X/1
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

King Hang Tommy Mau (KHT)

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.

Donja Karimlou (D)

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.

David Barneda (D)

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.
Signalling Programme, The Babraham Institute, Cambridge, CB22 3AT, UK.

Vincent Brochard (V)

Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, 78350, France.
École Nationale Vétérinaire d'Alfort, BREED, Maison-Alfort, 94700, France.

Christophe Royer (C)

Institute of Developmental & Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Oxford, OX3 7TY, UK.

Bryony Leeke (B)

MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

Roshni A de Souza (RA)

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.

Mélanie Pailles (M)

Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, 78350, France.
École Nationale Vétérinaire d'Alfort, BREED, Maison-Alfort, 94700, France.

Michelle Percharde (M)

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.
MRC London Institute of Medical Sciences (LMS), Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.

Shankar Srinivas (S)

Institute of Developmental & Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Old Road Campus, Oxford, OX3 7TY, UK.

Alice Jouneau (A)

Université Paris-Saclay, UVSQ, INRAE, BREED, Jouy-en-Josas, 78350, France.
École Nationale Vétérinaire d'Alfort, BREED, Maison-Alfort, 94700, France.

Mark Christian (M)

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.
Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK.

Véronique Azuara (V)

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. v.azuara@imperial.ac.uk.

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