iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer.

Autor: Park DS; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Kozaki T; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Tiwari SK; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Moreira M; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Khalilnezhad A; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Torta F; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore., Olivié N; Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France., Thiam CH; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Liani O; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Silvin A; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Phoo WW; Functional Proteomics Laboratory, SingMass National Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Gao L; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore., Triebl A; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore., Tham WK; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore., Gonçalves L; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Kong WT; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Raman S; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Zhang XM; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Dunsmore G; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Dutertre CA; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Lee S; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Ong JM; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Balachander A; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Khalilnezhad S; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Lum J; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Duan K; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Lim ZM; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Tan L; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Low I; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Utami KH; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research, Singapore, Singapore., Yeo XY; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research, Singapore, Singapore., Di Tommaso S; Oncoprot Platform, TBM-Core US 005, Bordeaux, France., Dupuy JW; Bordeaux Protéome, University of Bordeaux, Bordeaux, France., Varga B; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Karadottir RT; Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Veterinary Medicine, University of Cambridge, Cambridge, UK., Madathummal MC; A*STAR Microscopy Platform Electron Microscopy, Research Support Centre, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Bonne I; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Malleret B; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; A*STAR Microscopy Platform Electron Microscopy, Research Support Centre, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Binte ZY; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Wei Da N; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Tan Y; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Wong WJ; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Zhang J; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research, Singapore, Singapore., Chen J; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Sobota RM; Functional Proteomics Laboratory, SingMass National Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore., Howland SW; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore., Ng LG; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Shanghai Immune Therapy Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China., Saltel F; Oncoprot Platform, TBM-Core US 005, Bordeaux, France., Castel D; INSERM U981, Molecular Predictors and New Targets in Oncology & Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Grill J; INSERM U981, Molecular Predictors and New Targets in Oncology & Département de Cancérologie de l'Enfant et de l'Adolescent, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Minard V; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Albani S; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore., Chan JKY; Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore., Thion MS; Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France., Jung SY; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Medical Science, College of Medicine, CHA University, Seongnam, Republic of Korea., Wenk MR; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore., Pouladi MA; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research, Singapore, Singapore.; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada., Pasqualini C; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France., Angeli V; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Cexus ONF; Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore, Singapore.; Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research, Singapore, Singapore.; School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK., Ginhoux F; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore, Singapore. florent_ginhoux@immunol.a-star.edu.sg.; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. florent_ginhoux@immunol.a-star.edu.sg.; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif, France. florent_ginhoux@immunol.a-star.edu.sg.; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore, Singapore. florent_ginhoux@immunol.a-star.edu.sg.; Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. florent_ginhoux@immunol.a-star.edu.sg.
Jazyk: angličtina
Zdroj: Nature [Nature] 2023 Nov; Vol. 623 (7986), pp. 397-405. Date of Electronic Publication: 2023 Nov 01.
DOI: 10.1038/s41586-023-06713-1
Abstrakt: Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain 1 . Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues 2-6 . The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development 7-10 . However, current approaches do not incorporate microglia or address their role in organoid maturation 11-21 . Here we generated microglia-sufficient brain organoids by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac) 22 . In organoid cocultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro) and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2 + lipid droplets that exported cholesterol and its esters, which were taken up by NPCs in the organoids. We also detected PLIN2 + lipid droplet-loaded microglia in mouse and human embryonic brains. Overall, our approach substantially advances current human brain organoid approaches by incorporating microglial cells, as illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPCs that leads to improved neurogenesis.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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