PXD018352

PXD018352 is an original dataset announced via ProteomeXchange.

Title	Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters
Description	Tissue homeostasis and regeneration require activation and subsequent lineage commitment of tissue-resident stem cells (SCs). These state changes are controlled by epigenetic barriers. Using hair follicle stem cells (HFSCs) as paradigm, we studied how aging impacts the chromatin landscape and function of mammalian SCs. Analyses of genome-wide chromatin accessibility revealed that aged HFSCs displayed widespread reduction of chromatin accessibility specifically at key SC self-renewal and differentiation genes that were characterized by bivalent promoters carrying both activating and repressive chromatin marks. Consistently, aged HFSCs showed reduced self-renewing capacity and attenuated ability to activate expression of these bivalent genes upon regeneration. These functional defects were niche-dependent as transplantation of aged HFSCs into young recipients or into ex vivo niches restored SC functions and transcription of poised genes. Mechanistically, aged HFSC niche displayed wide-spread alterations in extracellular matrix composition and mechanics, resulting in compressive forces on SCs and subsequent transcriptional repression, leading to loss of bivalent promoters. Tuning tissue mechanics both in vivo and in vitro recapitulated age-related SC changes, implicating niche mechanics as a central regulator of genome organization and function leading to age-dependent SC exhaustion.
HostingRepository	PRIDE
AnnounceDate	2021-05-07
AnnouncementXML	Submission_2021-05-06_22:37:01.277.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ilian Atanassov
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-03 06:06:30	ID requested
⏵ 1	2021-05-06 22:37:01	announced

Dataset with its publication pending

submitter keyword: hair follicle stem cells, skin, TMT, Orbitrap Lumos

Sara Wickström
contact affiliation	Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), University of Cologne, 50931 Cologne, Germany Helsinki Institute of Life Science and Wihuri Research Institute, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland Stem Cells and Metabolism Research Program, Faculty of Medicine, University of Helsinki, 00290 Helsinki Finland
contact email	sara.wickstrom@helsinki.fi
lab head
Ilian Atanassov
contact affiliation	Max Planck Institute for Biology of Aging
contact email	Ilian.Atanassov@age.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/2021/05/PXD018352

PRIDE project URI

• PRIDE
  1. PXD018352
     1. Label: PRIDE project
     2. Name: Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters