PXD018352 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_05:21:41.838.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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-03 06:06:30 | ID requested | |
1 | 2021-05-06 22:37:01 | announced | |
⏵ 2 | 2024-10-22 05:21:42 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: TMT, skin,hair follicle stem cells, Orbitrap Lumos |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018352
- Label: PRIDE project
- Name: Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters