PXD044406-1

PXD044406 is an original dataset announced via ProteomeXchange.

Title	Proteomic analysis of human brain organoids
Description	Microglia are specialised brain-resident macrophages that arise from primitive macrophages colonising the embryonic brain. Microglia contribute to multiple aspects of brain development, but their precise roles in early human brain remain poorly understood due to limited access to relevant tissues. The generation of brain organoids from induced human pluripotent stem cells (iPSC) recapitulates some key features of human embryonic brain development, but current approaches do not incorporate microglia and thus are lacking. Here, we generated microglia-sufficient brain organoids by co-culturing brain organoids with primitive-like macrophages generated from the same human iPSC (iMac). In organoid co-cultures, 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 NPC in the organoids. We also detected PLIN2+ lipid droplet-loaded microglia in mouse and human embryonic brain. Overall, our approach significantly advances current human brain organoid approaches by incorporating microglial cells, illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPC leading to improved neurogenesis.
HostingRepository	PRIDE
AnnounceDate	2025-11-26
AnnouncementXML	Submission_2025-11-26_06:48:32.400.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dupuy Jean-William
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-07 02:51:36	ID requested
⏵ 1	2025-11-26 06:48:33	announced

Park DS, Kozaki T, Tiwari SK, Moreira M, Khalilnezhad A, Torta F, Olivi, é N, Thiam CH, Liani O, Silvin A, Phoo WW, Gao L, Triebl A, Tham WK, Gon, ç, alves L, Kong WT, Raman S, Zhang XM, Dunsmore G, Dutertre CA, Lee S, Ong JM, Balachander A, Khalilnezhad S, Lum J, Duan K, Lim ZM, Tan L, Low I, Utami KH, Yeo XY, Di Tommaso S, Dupuy JW, Varga B, Karadottir RT, Madathummal MC, Bonne I, Malleret B, Binte ZY, Wei Da N, Tan Y, Wong WJ, Zhang J, Chen J, Sobota RM, Howland SW, Ng LG, Saltel F, Castel D, Grill J, Minard V, Albani S, Chan JKY, Thion MS, Jung SY, Wenk MR, Pouladi MA, Pasqualini C, Angeli V, Cexus ONF, Ginhoux F, iPS-cell-derived microglia promote brain organoid maturation via cholesterol transfer. Nature, 623(7986):397-405(2023) [pubmed]

10.1038/s41586-023-06713-1;

submitter keyword: organoids,Brain, quantitative proteome, microglia

Florent Ginhoux
contact affiliation	Singapore Immunology Network (SIgN), Agency for Science, Technology and Research, Singapore 138648, Singapore
contact email	florent_ginhoux@immunol.a-star.edu.sg
lab head
Dupuy Jean-William
contact affiliation	OncoProt plateform, UAR TBMCore CNRS 3427 INSERM US005 University of Bordeaux
contact email	jean-william.dupuy@u-bordeaux.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD044406

PRIDE project URI

• PRIDE
  1. PXD044406
     1. Label: PRIDE project
     2. Name: Proteomic analysis of human brain organoids