PXD047573

PXD047573 is an original dataset announced via ProteomeXchange.

Title	Sphingolipid metabolism orchestrates the establishment of the adult hair follicle stem cell niche to control skin homeostasis
Description	Bioactive sphingolipids serve as an essential building block of membranes, forming a selective barrier ensuring subcellular compartmentalization and facilitating cell type-specific intercellular communication through regulation of the plasma membrane receptor repertoire. How the cell type-specific lipid compositions are achieved and what is their functional significance in tissue morphogenesis and maintenance has remained unclear. Here, we identify a stem-cell specific role for ceramide synthase 4 (CerS4) in orchestrating fate decisions in the skin epidermis. Deletion of CerS4 in the epidermis prevents the effective establishment of the adult hair follicle bulge stem cell (HFSCs) niche due to altered differentiation trajectories of HFSC precursors towards upper hair follicle and inner bulge fates. Mechanistically, the HFSC differentiation defects arise from a stem cell intrinsic imbalance of key ceramides and sphingolipids, and associated hyperactivity of canonical Wnt signaling. The lack of HFSCs leads to disruption of hair follicle architecture and hair follicle barrier function, ultimately triggering a Th2-dominated immune infiltration closely resembling human atopic dermatitis. This work uncovers a fundamental role for a cell state-specific sphingolipid profile in epidermal stem cell homeostasis and the role of an intact stem cell niche in maintaining an intact skin barrier.
HostingRepository	PRIDE
AnnounceDate	2025-01-23
AnnouncementXML	Submission_2025-01-23_05:01:06.780.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hannes Drexler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-06 07:28:36	ID requested
⏵ 1	2025-01-23 05:01:07	announced

10.1083/JCB.202403083;

submitter keyword: stem cells, atopic dermatitis, proteomics, skin, mass spectrometry, differentiation, hair follicle, ceramide synthase 4, Wnt signaling, sphingolipids

Hannes C. A. Drexler
contact affiliation	Max Planck Institute for Molecular Biomedicine Bioanalytical Mass Spectrometry Röntgenstr. 20 48159 Münster Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliation	Bioanalytical Mass Spectrometry, Max Planck Insitute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany
contact email	hannes.drexler@mpi-muenster.mpg.de
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/2025/01/PXD047573

PRIDE project URI

• PRIDE
  1. PXD047573
     1. Label: PRIDE project
     2. Name: Sphingolipid metabolism orchestrates the establishment of the adult hair follicle stem cell niche to control skin homeostasis