Universität zu Köln

Koester, Janis ORCID: 0000-0002-5274-0591, Miroshnikova, Yekaterina A., Ghatak, Sushmita, Chacon-Martinez, Carlos Andres, Morgner, Jessica ORCID: 0000-0001-6374-8639, Li, Xinping ORCID: 0000-0002-7427-0017, Atanassov, Ilian ORCID: 0000-0001-8259-2545, Altmueller, Janine, Birk, David E., Koch, Manuel ORCID: 0000-0002-2962-7814, Bloch, Wilhelm, Bartusel, Michaela, Niessen, Carien M. ORCID: 0000-0002-4892-9391, Rada-Iglesias, Alvaro ORCID: 0000-0001-7137-1341 and Wickstroem, Sara A. (2021). Niche stiffening compromises hair follicle stem cell potential during ageing by reducing bivalent promoter accessibility. Nat. Cell Biol., 23 (7). S. 771 - 797. BERLIN: NATURE RESEARCH. ISSN 1476-4679

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Abstract

Tissue turnover requires activation and lineage commitment of tissue-resident stem cells (SCs). These processes are impacted by ageing, but the mechanisms remain unclear. Here, we addressed the mechanisms of ageing in murine hair follicle SCs (HFSCs) and observed a widespread reduction in chromatin accessibility in aged HFSCs, particularly at key self-renewal and differentiation genes, characterized by bivalent promoters occupied by active and repressive chromatin marks. Consistent with this, aged HFSCs showed reduced ability to activate bivalent genes for efficient self-renewal and differentiation. These defects were niche dependent as the transplantation of aged HFSCs into young recipients or synthetic niches restored SC functions. Mechanistically, the aged HFSC niche displayed widespread alterations in extracellular matrix composition and mechanics, resulting in mechanical stress and concomitant transcriptional repression to silence promoters. As a consequence, increasing basement membrane stiffness recapitulated age-related SC changes. These data identify niche mechanics as a central regulator of chromatin state, which, when altered, leads to age-dependent SC exhaustion. Koester et al. show that, as hair follicle stem cells age, their ability to activate bivalent genes for self-renewal and differentiation is reduced due to increased niche stiffening and subsequent epigenetic effects.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Koester, Janis UNSPECIFIED orcid.org/0000-0002-5274-0591 UNSPECIFIED Miroshnikova, Yekaterina A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ghatak, Sushmita UNSPECIFIED UNSPECIFIED UNSPECIFIED Chacon-Martinez, Carlos Andres UNSPECIFIED UNSPECIFIED UNSPECIFIED Morgner, Jessica UNSPECIFIED orcid.org/0000-0001-6374-8639 UNSPECIFIED Li, Xinping UNSPECIFIED orcid.org/0000-0002-7427-0017 UNSPECIFIED Atanassov, Ilian UNSPECIFIED orcid.org/0000-0001-8259-2545 UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Birk, David E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED orcid.org/0000-0002-2962-7814 UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Bartusel, Michaela UNSPECIFIED UNSPECIFIED UNSPECIFIED Niessen, Carien M. UNSPECIFIED orcid.org/0000-0002-4892-9391 UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED orcid.org/0000-0001-7137-1341 UNSPECIFIED Wickstroem, Sara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597805
DOI:	10.1038/s41556-021-00705-x
Journal or Publication Title:	Nat. Cell Biol.
Volume:	23
Number:	7
Page Range:	S. 771 - 797
Date:	2021
Publisher:	NATURE RESEARCH
Place of Publication:	BERLIN
ISSN:	1476-4679
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HISTONE MODIFICATIONS; IN-VIVO; CHROMATIN; DISTINCT; BINDING; MICE Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59780