PXD048559

PXD048559 is an original dataset announced via ProteomeXchange.

Title	Multi-omic analysis of guided and unguided forebrain organoids
Description	Neural organoids are invaluable model systems for studying neurodevelopment and neurological diseases. For this purpose, reproducible differentiation protocols are needed that minimize inter-organoid variability whilst generating neural organoids that physiologically resemble the brain area of interest. Currently, two main approaches are used: guided, where the differentiation towards neuroectoderm and subsequently specific CNS regions is driven by applying extrinsic signalling molecules, and unguided, where the intrinsic capability of pluripotent stem cells to generate neuroectoderm without external signalling is promoted. Despite the importance for the field, the resulting differences between these models have not been directly investigated. To obtain an unbiased comparison, we performed a multi-omic analysis of forebrain organoids generated using a guided and unguided approach focusing on proteomic, lipidomic and metabolomic differences. Furthermore, we characterised differences in phosphorylation and sialylation states of proteins, two key post-translational modifications (PTMs) in neurodevelopment, and performed single cell transcriptomics (scRNAseq). The multi-omic analysis revealed considerable differences in neuronal-, synaptic and glial content, indicating that guided forebrain organoids contain a larger proportion of neurons, including GABAergic interneurons, and synapses whereas unguided organoids contain significantly more GFAP+ cells and choroid plexus. Furthermore, substantial differences in mitochondrial- and metabolic profiles were identified, pointing to increased levels of oxidative phosphorylation and fatty acid β-oxidation in unguided forebrain organoids and a higher reliance on glycolysis in guided forebrain organoids. Overall, our study comprises a thorough description of the multi-omic differences arising when generating guided and unguided forebrain organoids and provide an important resource for the organoid field studying neurodevelopment and -disease.
HostingRepository	PRIDE
AnnounceDate	2026-02-25
AnnouncementXML	Submission_2026-02-25_08:58:41.628.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Helle Bogetofte
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; N-acetylneuraminylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-15 05:24:14	ID requested
⏵ 1	2026-02-25 08:58:42	announced

Ø, hlenschl, æ, ger MS, Jensen P, Havelund JF, Schmidt SI, Mohamed FA, Sutcliffe M, Elmkvist SB, Criscuolo L, Wingett SW, Chiaradia I, Bayram E, Nicolaisen JAA, Jakobsen LA, Brewer J, Benros ME, Freude K, F, æ, rgeman NJ, Lancaster MA, Larsen MR, Bogetofte H, Multi-omic analysis of guided and unguided forebrain organoids reveals differences in cellular composition and metabolic profiles. Cell Rep Methods, 6(2):101295(2026) [pubmed]

10.1016/j.crmeth.2025.101295;

submitter keyword: Human, organoids, Orbitrap Exploris, forebrain, sialylation, phosphorylation

Martin Røssel Larsen
contact affiliation	Department of Biochemistry and Molecular Biology University of Southern Denmark
contact email	mrl@bmb.sdu.dk
lab head
Helle Bogetofte
contact affiliation	University of Southern Denmark
contact email	hbogetofte@bmb.sdu.dk
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/2026/02/PXD048559

PRIDE project URI

• PRIDE
  1. PXD048559
     1. Label: PRIDE project
     2. Name: Multi-omic analysis of guided and unguided forebrain organoids