PXD038909

PXD038909 is an original dataset announced via ProteomeXchange.

Title	Spatial lipidomic profiling of mouse joint tissue demonstrates the essential role of PHOSPHO1 in growth plate homeostasis
Description	Lipids play a crucial role in signalling and metabolism, regulating the development and maintenance of the skeleton. Membrane lipids have been hypothesised to act as intermediates upstream of orphan phosphatase 1 (PHOSPHO1), a major contributor to phosphate generation required for bone mineralisation. Here, we spatially resolve the lipid atlas of the healthy mouse knee and demonstrate the effects of PHOSPHO1 ablation on the growth plate lipidome. Lipids spanning 17 subclasses were mapped across the knee joints of healthy juvenile and adult mice using matrix-assisted laser desorption ionisation imaging mass spectrometry (MALDI-IMS), with annotation supported by shotgun lipidomics. Multivariate analysis identified 96 and 80 lipid ions with differential abundances across joint tissues in juvenile and adult mice respectively. In both ages, marrow was enriched in phospholipid platelet activating factors (PAFs) and related metabolites, cortical bone had a low lipid content, while lysophospholipids were strikingly enriched in the growth plate, an active site of mineralisation and PHOSPHO1 activity. Spatially-resolved profiling of PHOSPHO1-knockout (KO) mice across the resting, proliferating, and hypertrophic growth plate zones revealed 272, 306, and 296 significantly upregulated, and 155, 220 and 190 significantly downregulated features, respectively, relative to wild type (WT) controls. Of note, phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, lysophosphatidylethanolamine and phosphatidylethanolamine derived lipid ions were upregulated in PHOSPHO1-KO versus WT. Our imaging pipeline has established a spatially-resolved lipid signature of joint tissues and has demonstrated that PHOSPHO1 ablation significantly alters the growth plate lipidome, highlighting an essential role of the PHOSPHO1-mediated membrane phospholipid metabolism in lipid and bone homeostasis.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:44:59.101.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jordan Tzetkov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	SYNAPT G2-Si

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-19 03:11:18	ID requested
1	2023-04-19 16:26:42	announced
⏵ 2	2023-11-14 08:44:59	announced	2023-11-14: Updated project metadata.

Tzvetkov J, Stephen LA, Dillon S, Millan JL, Roelofs AJ, De Bari C, Farquharson C, Larson T, Genever P, Spatial Lipidomic Profiling of Mouse Joint Tissue Demonstrates the Essential Role of PHOSPHO1 in Growth Plate Homeostasis. J Bone Miner Res, 38(5):792-807(2023) [pubmed]

submitter keyword: mouse, MALDI-IMS, PHOSPHO1, matrix mineralisation, disorders of calcium or phosphate metabolism, lipids, knee joint, growth plate, bone modelling and remodelling

Paul Gilbert Genever
contact affiliation	Professor Department of Biology University of York York United Kingdom
contact email	paul.genever@york.ac.uk
lab head
Jordan Tzetkov
contact affiliation	University of York
contact email	j.tzvetkov1995@gmail.com
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/2023/04/PXD038909

PRIDE project URI

• PRIDE
  1. PXD038909
     1. Label: PRIDE project
     2. Name: Spatial lipidomic profiling of mouse joint tissue demonstrates the essential role of PHOSPHO1 in growth plate homeostasis