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https://doi.org/10.1038/s41586-023-06713-1
Title: | iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer | Authors: | Park, Dong Shin Kozaki, Tatsuya Tiwari, Satish Kumar Moreira, Marco Khalilnezhad, Ahad Torta, Federico Olivie, Nicolas Thiam, Chung Hwee Liani, Oniko Silvin, Aymeric Phoo, Wint Wint Gao, Liang Triebl, Alexander Tham, Wai Kin Goncalves, Leticia Kong, Wan Ting Raman, Sethi Zhang, Xiao Meng Dunsmore, Garett Dutertre, Charles Antoine Lee, Salanne Ong, Jia Min Balachander, Akhila Khalilnezhad, Shabnam Lum, Josephine Duan, Kaibo Lim, Ze Ming Tan, Leonard Low, Ivy Utami, Kagistia Hana Yeo, Xin Yi Di Tommaso, Sylvaine Dupuy, Jean-William Varga, Balazs Karadottir, Ragnhildur Thora Madathummal, Mufeeda Changaramvally Bonne, Isabelle Malleret, Benoit Binte, Zainab Yasin Da, Ngan Wei Tan, Yingrou Wong, Wei Jie Zhang, Jinqiu Chen, Jinmiao Sobota, Radoslaw M Howland, Shanshan W Ng, Lai Guan Saltel, Frederic Castel, David Grill, Jacques Minard, Veronique Albani, Salvatore Chan, Jerry KY Thion, Morgane Sonia Jung, Sang Yong Wenk, Markus R Pouladi, Mahmoud A Pasqualini, Claudia Angeli, Veronique Cexus, Olivier NF Ginhoux, Florent |
Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics PLURIPOTENT STEM-CELLS CEREBRAL ORGANOIDS ADULT MICROGLIA IN-VIVO NEUROGENESIS NEURONS DIFFERENTIATION ASTROCYTES FEATURES CORTEX |
Issue Date: | 9-Nov-2023 | Publisher: | NATURE PORTFOLIO | Citation: | Park, Dong Shin, Kozaki, Tatsuya, Tiwari, Satish Kumar, Moreira, Marco, Khalilnezhad, Ahad, Torta, Federico, Olivie, Nicolas, Thiam, Chung Hwee, Liani, Oniko, Silvin, Aymeric, Phoo, Wint Wint, Gao, Liang, Triebl, Alexander, Tham, Wai Kin, Goncalves, Leticia, Kong, Wan Ting, Raman, Sethi, Zhang, Xiao Meng, Dunsmore, Garett, Dutertre, Charles Antoine, Lee, Salanne, Ong, Jia Min, Balachander, Akhila, Khalilnezhad, Shabnam, Lum, Josephine, Duan, Kaibo, Lim, Ze Ming, Tan, Leonard, Low, Ivy, Utami, Kagistia Hana, Yeo, Xin Yi, Di Tommaso, Sylvaine, Dupuy, Jean-William, Varga, Balazs, Karadottir, Ragnhildur Thora, Madathummal, Mufeeda Changaramvally, Bonne, Isabelle, Malleret, Benoit, Binte, Zainab Yasin, Da, Ngan Wei, Tan, Yingrou, Wong, Wei Jie, Zhang, Jinqiu, Chen, Jinmiao, Sobota, Radoslaw M, Howland, Shanshan W, Ng, Lai Guan, Saltel, Frederic, Castel, David, Grill, Jacques, Minard, Veronique, Albani, Salvatore, Chan, Jerry KY, Thion, Morgane Sonia, Jung, Sang Yong, Wenk, Markus R, Pouladi, Mahmoud A, Pasqualini, Claudia, Angeli, Veronique, Cexus, Olivier NF, Ginhoux, Florent (2023-11-09). iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer. NATURE 623 (7986). ScholarBank@NUS Repository. https://doi.org/10.1038/s41586-023-06713-1 | Abstract: | Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain1. 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 tissues2–6. The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development7–10. However, current approaches do not incorporate microglia or address their role in organoid maturation11–21. 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. | Source Title: | NATURE | URI: | https://scholarbank.nus.edu.sg/handle/10635/247854 | ISSN: | 1476-4687 0028-0836 |
DOI: | 10.1038/s41586-023-06713-1 |
Appears in Collections: | Elements Staff Publications |
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