Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles

ABSTRACT: Aging organs functionally and structurally decline with the loss of their regenerative capabilities, yet the existence of distinct cell division programs that determine organ fates is unknown. Hair follicles, mammalian mini-organs that grow hair, miniaturize by aging. Here we report that hair follicle regeneration and aging are driven by distinct cell division types of hair follicle stem cells (HFSCs). Cell fate tracing and cell division axis analysis in mice revealed that HFSCs undergo symmetric and asymmetric cell divisions to generate a new bulge, yet preferentially provoke “stress-responsive type” asymmetric cell divisions that generate aberrantly differentiating cells upon age/stress. That dynamic program with repetitive divisions efficiently eradicates those cells through defective association and stabilization of a hemidesmosomal protein COL17A1 and a cell-polarity-protein aPKCλ in HFSCs, thereby causing organ aging. The forced stabilization of COL17A1 rescued organ aging through aPKCλ stabilization. These results demonstrate that distinct cell division programs govern tissue/organ fates.

ORGANISM(S): Mus musculus

PROVIDER: GSE124119 | GEO | 2020/12/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hair follicle aging is driven by transepidermal stem cell elimination via COL17A1 proteolysis

Project description:Hair loss is one of the typical aging phenotypes in mammals, yet the underlying mechanism(s) is unclear. Here we report that hair follicle stem cell (HFSC) aging causes the stepwise miniaturization of hair follicles and eventual hair loss both in wild-type mice and in humans. In vivo fate analysis of HFSCs revealed that the DNA damage response in HFSCs causes proteolysis of Type XVII Collagen (COL17A1/BP180) to trigger “HFSC aging”, characterized by their loss of stemness signature and epidermal commitment. Those aged HFSCs are cyclically eliminated from the skin through their terminal epidermal differentiation, thereby causing hair follicle miniaturization. That process can be recapitulated by Col17a1 deficiency and prevented by forced maintenance of COL17A1 in HFSCs, demonstrating that stem cell homeostasis is the keystone against ultimate execution of the tissue/organ aging program.

2015-12-01 | GSE72863 | GEO

Obesity accelerates hair thinning by stem cell-centric converging mechanism [RNA-seq]

Project description:Obesity, a worldwide epidemic, predisposes to many ageing-associated diseases, yet its exact impact on organ dysfunction is largely unknown. Hair follicles, mini-epithelial organs that grow hair, miniaturize by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs). Here, we report that obesity-induced stress such as by high-fat diet (HFD) feeding primarily targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days directs activated HFSCs toward epidermal keratinization by generating excessive reactive oxygen species yet retains HFSC pools in young mice. Integrative analysis with stem cell fate tracing, epigenetic analysis and reverse genetics revealed that further feeding of HFD subsequently induces lipid droplets and NF-B activation within HFSCs via autocrine/paracrine IL1R signaling. Those integrated factors converge on the profound inhibition of Sonic hedgehog (Shh) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs through their aberrant differentiation and inducing hair follicle miniaturization and eventual hair loss. Conversely, Shh activation by transgenes or compounds rescues HFD-induced hair loss. These data collectively demonstrate that stem cell inflammageing induced by obesity robustly represses organ regeneration signals to accelerate the mini-organ miniaturization, and suggests the importance of daily prevention of organ dysfunction.

2021-04-14 | GSE169173 | GEO

Obesity accelerates hair thinning in stem cell-centric converging mechanism

Project description:Obesity, a worldwide epidemic, predisposes to many ageing-associated diseases, yet its exact impact on organ dysfunction is largely unknown. Hair follicles, mini-epithelial organs that grow hair, miniaturize by ageing to cause hair loss through the depletion of hair follicle stem cells (HFSCs). Here, we report that obesity-induced stress such as by high-fat diet (HFD) feeding primarily targets HFSCs to accelerate hair thinning. Chronological gene expression analysis revealed that HFD feeding for four consecutive days directs activated HFSCs toward epidermal keratinization by generating excessive reactive oxygen species yet retains HFSC pools in young mice. Integrative analysis with stem cell fate tracing, epigenetic analysis and reverse genetics revealed that further feeding of HFD subsequently induces lipid droplets and NF-κB activation within HFSCs via autocrine/paracrine IL1R signaling. Those integrated factors converge on the profound inhibition of Sonic hedgehog (Shh) signal transduction in HFSCs, thereby further depleting lipid-laden HFSCs from the skin surface and inducing hair follicle miniaturization and eventual hair loss. Conversely, Shh activation by transgenes or compounds rescues HFD-induced hair loss. These data collectively demonstrate that stem cell inflammageing induced by obesity robustly represses organ regeneration signals to accelerate the mini-organ miniaturization, and indicates suggests the importance of daily prevention of organ dysfunction.

2021-04-14 | GSE131958 | GEO

Nfatc1 Orchestrates Aging in Hair Follicle Stem Cells

Project description:Mouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by hair follicle stem cells (HFSCs). We used ChIP-seq to unfold genome-wide chromatin landscapes of Nfatc1 and dissect the biological relevence of its upstream BMP signaling in HFSC aging. Telogen quiescent hair follicle stem cells (HFSCs) were FACS-purified for ChIP-sequcencing.

2013-11-14 | E-GEOD-52328 | biostudies-arrayexpress

A mechanism for the segregation of age in mammalian neural stem cells

Project description:Across life neural stem cells (NSCs) generate new neurons in the mammalian brain through asymmetric neurogenic and self-renewing cell divisions. However, the cellular mechanisms underlying NSC asymmetry remain unknown. Using fluorescence loss in photobleaching (FLIP) we here show that NSCs in vitro and within the developing forebrain generate a lateral diffusion barrier during cell division resulting in asymmetric segregation of cellular components. The strength of the diffusion barrier is dynamically regulated with age and depends on the proper function of lamin-associated nuclear envelope constituents. Strikingly, age-associated or experimental impairment of the diffusion barrier disrupts asymmetric segregation of damaged proteins, a product of aging. Thus, the data presented here identify a mechanism how age is asymmetrically distributed during somatic stem cell division. For microarray analysis we analysed gene expression in cells derived from the hippocampi of 6 week old (young) or 9 month old (old) male C57BL/6JRj mice. 6 samples were analyzed YoungNSC, 3 replicates OldNSC, 3 replicates

2015-09-22 | E-GEOD-61367 | biostudies-arrayexpress

Functional stem cell aging dictated by skin tissue microenvironment

Project description:Organismal aging in mammals is manifested with architectural alteration and functional decline of multiple organs throughout the body. In aged skin, hairs are sparse, which has led to the hypothesis that the hair follicle stem cells (HFSCs) undergo epidermal differentiation during aging. Here, we employ single cell analysis to interrogate aging-related changes in the HFSCs. Unexpectedly, HFSCs maintain their lineage fidelity and show no signs of shifting to an epidermal fate. Despite maintaining lineage identity, HFSCs do show prevalent transcriptional changes in extracellular matrix genes. Of importance, these HFSC changes are accompanied by profound architectural perturbations in the aging stem cell niche. Upon surveying the dermis from young and aged skin, we also observe age-related changes in many non-epithelial cell types, including resident immune cells, sensory neurons, arrector pili muscles, and blood vessels – all of which have been previously associated with abilities to modulate hair follicle regeneration. Consistent with both intrinsic and extrinsic alterations in stem cell: niche communications, we find that in response to skin wounding, aged HFSCs repair the epidermis, but are defective in hair follicle regeneration. Intriguingly, whereas aged dermis cannot support young HFSCs, aged HFSCs can be rescued when supported by young dermis. Together, these findings favor a model where skin tissue microenvironment plays a dominant role in dictating the molecular properties and activities of HFSCs.

2019-12-31 | GSE124901 | GEO

A mechanism for the segregation of age in mammalian neural stem cells

2015-09-22 | GSE61367 | GEO

A molecular framework for control of oriented cell division in the Arabidopsis embryo

Project description:Premitotic control of cell division orientation is critical for plant development, as cell walls prevent extensive cell remodelling or migration. Whilst many divisions are proliferative and add cells to existing tissues, some divisions are formative, and generate new tissue layers or growth axes. Such formative divisions are often asymmetric in nature, producing daughters with different fates. We have previously shown that in the Arabidopsis thaliana embryo, developmental asymmetry is correlated with geometric asymmetry, creating daughter cells of unequal volume. Such divisions are generated by division planes that deviate from a default “minimal surface area” rule. Inhibition of auxin response leads to reversal to this default, yet the mechanisms underlying division plane choice in the embryo have been unclear. Here we show that auxin-dependent division plane control involves alterations in cell geometry, but not in cell polarity or nuclear position. Through transcriptome profiling, we find that auxin regulates genes controlling cell wall and cytoskeleton properties. We confirm the involvement of microtubule (MT)-binding proteins in embryo division control. Topology of both MT and Actin cytoskeleton depend on auxin response, and genetically controlled MT or Actin depolymerization in embryos leads to disruption of asymmetric divisions, including reversion to the default. Our work shows how auxin-dependent control of MT- and Actin cytoskeleton properties interacts with cell geometry to generate asymmetric divisions during the earliest steps in plant development. Transcriptional profiling of Col-0 vs bdl 8-cell Arabidopsis embryos

2021-10-05 | GSE165986 | GEO

Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles

Project description:Distinct types of stem cell divisions determine organ regeneration and aging in hair follicles

| PRJNA510803 | ENA

Signaling couples hair follicle stem cell quiescence with reduced histone H3K4/K9/K27me3 for proper tissue homeostasis

Project description:Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T cell progenitors. We used mouse hair follicle stem cells (HFSCs) at two different hair cycle stages (early anagen and late catagen) to compare the genome-wide changes in the levels of histone modification marks H3K4me3, H3K9me3, and H3K27me3. Hair follicle stem cells from Early Anagen (EA-HFSCs) and Late Catagen (LC-HFSCs), and their non-HFSCs counterparts (nEA-HFSCs and nLC-HFSCs), were FACS-isolated for Chromatin Immunoprecipitation followed by sequencing (ChIP-seq) analysis of H3K4me3, H3K9me3, and H3K27me3.

2016-04-13 | E-GEOD-78749 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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