PXD050841

PXD050841 is an original dataset announced via ProteomeXchange.

Title	Multi-Omic analyses reveal aberrant differentiation trajectory with WNT1 Loss-of-Function in type XV osteogenesis imperfecta
Description	Osteogenesis imperfecta (OI) is a serious genetic bone disorder characterized by congenital low bone mass, deformity and frequent fractures. Type XV OI is a moderate to severe form of skeletal dysplasia caused by WNT1 mutations. In this cohort study from southern China, we summarized the clinical phenotypes of patients with WNT1 mutations and found the proportion of type XV patients was around 10.3% (25 out of 243) with diverse phenotypic spectrums. Functional assays indicated that mutations of WNT1 significantly impaired its secretion and effective activity, leading to moderate to severe clinical manifestations, porous bone structure and enhanced osteoclastic activities. Analysis of proteomic data from human skeleton indicated that the expression of SOST was dramatically reduced in type XV patients. Single-cell transcriptome data generated from human tibia samples revealed aberrant differentiation trajectory of skeletal progenitors and impaired maturation of osteocytes, resulting in excessive CXCL12+ progenitors and abnormal cell populations with adipogenic characteristics. The integration of multi-omics data from human skeleton delineates how WNT1 regulates the differentiation and maturation of skeletal progenitors, which will provide a new direction for the treatment strategy of type XV osteogenesis imperfecta and relative low bone mass diseases such as early onset osteoporosis.
HostingRepository	PRIDE
AnnounceDate	2024-10-17
AnnouncementXML	Submission_2024-10-17_05:13:14.324.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peikai Chen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-20 19:27:50	ID requested
⏵ 1	2024-10-17 05:13:15	announced

Tan Z, Chen P, Zhang J, Shek HT, Li Z, Zhou X, Zhou Y, Yin S, Dong L, Feng L, Wong JSH, Gao B, To MKT, Multi-omics analyses reveal aberrant differentiation trajectory with WNT1 loss-of-function in type XV osteogenesis imperfecta. J Bone Miner Res, 39(9):1253-1267(2024) [pubmed]

10.1093/jbmr/zjae123;

submitter keyword: Human, bone, Osteogenesis imperfecta

Michael Kai Tsun To
contact affiliation	Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
contact email	tanzj@hku-szh.org
lab head
Peikai Chen
contact affiliation	The University of Hong Kong - Shenzhen Hospital
contact email	pkchen@hku-szh.org
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/2024/10/PXD050841

PRIDE project URI

• PRIDE
  1. PXD050841
     1. Label: PRIDE project
     2. Name: Multi-Omic analyses reveal aberrant differentiation trajectory with WNT1 Loss-of-Function in type XV osteogenesis imperfecta