Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE248615 | GEO | 2025/07/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma [array]

Project description:The exposome, an individual’s lifelong environmental exposure, profoundly impacts health. Somatic tissues undergo functional decline with age, exhibiting characteristic ageing phenotypes including hair graying and cancer. However, the specific genotoxins, signals and cellular mechanisms underlying each phenotype remain largely unknown. Here, we report that melanocyte stem cells (McSCs) and their niche coordinately determine individual stem cell fate through antagonistic, stress-responsive pathways, depending on the type of genotoxic damage incurred. McSC fate-tracking in mice revealed that McSCs undergo cellular senescence-associated differentiation (seno-differentiation) in response to DNA double-strand breaks (DSBs), resulting in their selective depletion and hair graying, and effectively protecting against melanoma. Conversely, carcinogens can suppress McSC seno-differentiation, even in DSB-harboring cells, by activating arachidonic acid metabolism and the niche-derived KIT ligand, thereby promoting McSC self-renewal. Collectively, the fate of individual stem cell clones - expansion versus exhaustion - cumulatively and antagonistically governs ageing phenotypes through interaction with the niche.

2025-07-07 | GSE158611 | GEO

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma [array]

2025-07-07 | GSE248613 | GEO

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma [scRNA-Seq]

2025-07-07 | GSE252031 | GEO

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma [RNA-Seq]

2025-07-07 | GSE249074 | GEO

Antagonistic stem cell fates under stress govern decisions between hair greying and melanoma [RNA-seq]

Project description:The incidence of diseases, including cancer, increases with age. While age-associated diseases with stem cell exhaustion are potentially antagonistic to cancer development1, the relationship between those is still largely unknown. Here, we report that melanocyte stem cells (McSCs) and their niche coordinately govern the antagonism between poliosis (hair graying) and melanoma. We found that McSCs undergo senescence-associated differentiation (seno-differentiation) in response to DNA double strand breaks (DSBs) such as by ionizing radiation (IR) and ageing upon their activation for self-renewal, leading to their depletion and resultant hair graying at the cost of cancer protection. RNA-seq and functional analysis of the skin exposed to different types of genotoxic stress revealed that activation of the p53-p21 axis and TBK1 pathway by DSBs within McSCs causes their depletion. Comparative analysis of the young vs. aged stem cell niche identified the KIT ligand (KITL/SCF) as a master niche factor for McSC self-renewal. Strikingly, co-exposure of the irradiated skin to carcinogens rescued hair graying by augmenting the secretory phenotype of niche cells to repress McSC seno-differentiation through the dual activation of KIT signaling and arachidonic acid pathway in McSCs. Collectively, our data provide concrete evidence for the phenotypic trade-off between ageing and cancer based on the niche.

2025-07-07 | GSE248614 | GEO