Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A hyper-quiescent chromatin state is a barrier to productive regeneration during aging. [RNA-Seq]

ABSTRACT: Epigenetic alterations are one of the key hallmarks of aging. Emerging evidence in model organisms, senescent cell cultures and limitedly, murine, and human tissue samples suggest local effects impacting genes and regulatory elements. However, how chromatin changes broadly affect euchromatin-heterochromatin balance, three-dimensional chromatin conformation, histone composition and global transcriptome has not been addressed. Furthermore, the cause and impact of these alterations on tissue function and age-related loss of regeneration is not well-understood. Here, using murine liver as a model for regeneration and an integrated multi-omics approach, we find that aged cells assume a severely repressed hyper-quiescent chromatin state characterized by a condensed chromatin, broad heterochromatinization driven by H3K27me3, global suppression of the transcriptome and inability of the chromatin to self-interact over long distances. Interestingly, concomitant targeted chromatin opening occurs over developmental gene promoters leading to loss of cell identity. We extend our findings to other quiescent tissues including human liver biopsies. Our findings reveal that global chromatin alterations promote a cellular state that is refractory to injury sensing and repair. Local chromatin changes compromise cellular identity. Together, this study provides possible explanations for age-related loss of regeneration and tissue function at the chromatin level.

ORGANISM(S): Mus musculus

PROVIDER: GSE185705 | GEO | 2023/03/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

A hyper-quiescent chromatin state is a barrier to productive regeneration during aging. [DNA-Seq]

Project description:Epigenetic alterations are one of the key hallmarks of aging. Emerging evidence in model organisms, senescent cell cultures and limitedly, murine, and human tissue samples suggest local effects impacting genes and regulatory elements. However, how chromatin changes broadly affect euchromatin-heterochromatin balance, three-dimensional chromatin conformation, histone composition and global transcriptome has not been addressed. Furthermore, the cause and impact of these alterations on tissue function and age-related loss of regeneration is not well-understood. Here, using murine liver as a model for regeneration and an integrated multi-omics approach, we find that aged cells assume a severely repressed hyper-quiescent chromatin state characterized by a condensed chromatin, broad heterochromatinization driven by H3K27me3, global suppression of the transcriptome and inability of the chromatin to self-interact over long distances. Interestingly, concomitant targeted chromatin opening occurs over developmental gene promoters leading to loss of cell identity. We extend our findings to other quiescent tissues including human liver biopsies. Our findings reveal that global chromatin alterations promote a cellular state that is refractory to injury sensing and repair. Local chromatin changes compromise cellular identity. Together, this study provides possible explanations for age-related loss of regeneration and tissue function at the chromatin level.

2023-03-19 | GSE185707 | GEO

A hyper-quiescent chromatin state is a barrier to productive regeneration during aging. [CUT&Tag ]

2023-03-17 | GSE185703 | GEO

A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Project description:Epigenetic alterations are a key hallmark of aging but have not been extensively explored in tissues. Here, using naturally aged murine liver as a model and extending study to other quiescent tissues, we find that aging is driven by temporal chromatin alterations that promote a refractory cellular state and compromise cellular identity. Using an integrated multi-omics approach and the first direct visualization of aged chromatin, we find that old cells show global H3K27me3-driven broad heterochromatinization and transcription suppression. At the local level, site-specific loss of H3K27me3 from promoters of genes encoding developmental transcription factors leads to expression in liver of non-hepatocyte markers. Interestingly, liver regeneration reverses H3K27me3 patterns and rejuvenates multiple molecular and physiological aspects of the aged liver.

2023-03-17 | GSE223480 | GEO

A hyper-quiescent chromatin state formed during aging is reversed by regeneration [ChIP-seq]

2023-03-17 | GSE185704 | GEO

Niche stiffening compromises stem cell potential during aging by reducing chromatin accessibility at bivalent promoters

Project 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.

2021-05-07 | PXD018352 | Pride

Fibrogenic cell plasticity blunts tissue regeneration and aggravates muscular dystrophy

Project description:Preservation of cell identity is necessary for homeostasis of most adult tissues. This process is challenged every time a tissue undergoes regeneration after stress or injury. In the lethal Duchenne muscular Dystrophy (DMD), skeletal muscle regenerative capacity declines gradually as fibrosis increases. Using genetically engineered-tracing mice, we demonstrate that in dystrophic muscle, specialized cells of muscular, endothelial and hematopoietic origins gain plasticity towards a fibrogenic fate via a TGFβ-mediated pathway. This results in loss of cellular identity and normal function, with deleterious consequences for regeneration. Furthermore, this fibrogenic process involves acquisition of a mesenchymal progenitor multipotent status, illustrating a link between fibrogenesis and gain of progenitor cell functions. As this plasticity was also observed in DMD patients, we propose that mesenchymal transitions impair regeneration and worsen diseases with a fibrotic component. TGFb exposure induced gene expression was measured after 4 days of treatment compared to untreated cells. Three independent experiments were performed both for the treatment and for the control

2015-04-09 | E-GEOD-67687 | biostudies-arrayexpress

Cell state transitions regulated by Slug are critical for tissue regeneration and tumor initiation [Agilent microarray samples]

Project description:Alterations that perturb differentiation and cell state transitions can lead to defects in development, function and the genesis of cancer. Studying cellular plasticity at high resolution and in real time has proven difficult using existing methods. Here, we use a quantitative approach to gain insights into cell state dynamics of normal mammary epithelial cells (MECs) and validate the model's predictions in vivo. In the absence of Slug/SNAI2, basal mammary progenitor cells transition into a luminal differentiation state, while luminal progenitor cells proliferate and expand; these changes result in abnormal mammary architecture and defects in tissue function. Loss of Slug also disrupts cellular plasticity leading to defects in tissue regeneration and the initiation of cancer. Mechanistically, Slug promotes cellular plasticity by recruiting the chromatin modifier, LSD1 (lysine specific demethylase 1), to promoters of lineage specific genes to represses transcription. Together, these finding demonstrate that Slug is necessary for cellular adaptation during tissue development and regeneration, and that transitioning back into a more primitive stem-like state is a prerequisite for tumor initiation. reference x sample

2014-06-23 | E-GEOD-54713 | biostudies-arrayexpress

Foxc1 reinforces quiescence in hair follicle stem cells

Project description:Quiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation. Poly(A)-enriched transcriptome RNA-seq on HFSCs isolated in WT and K14Cre cKO mice at anagen and early telogen stage of hair cycle.

2016-02-05 | E-GEOD-67404 | biostudies-arrayexpress

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (Micro-C XL)

Project description:Determining the conformation of chromatin in cells at the nucleosome level and its relationship to cellular processes has been a central challenge in biology. We show that in quiescent yeast, widespread transcriptional repression coincides with the local compaction of chromatin fibers into structures that are less condensed and more heteromorphic than canonical 30-nanometer forms. Acetylation or substitution of H4 tail residues decompacts fibers and leads to global transcriptional de-repression. Fiber decompaction also increases the rate of loop extrusion by condensin. These findings establish a role for H4 tail-dependent local chromatin fiber folding in regulating transcription and loop extrusion in cells. They also demonstrate the physiological relevance of canonical chromatin fiber folding mechanisms even in the absence of regular 30-nanometer structures.

2021-11-04 | GSE167019 | GEO

Chromatin Fiber Folding Represses Transcription and Loop Extrusion in Quiescent Cells (ChIP-Seq)

2021-11-04 | GSE167017 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data