Tier 4 — mechanistic

Dedifferentiation maintains melanocyte stem cells in a dynamic niche

Sun Q, Lee W, Hu H, Ogawa T, De Leon S, Katehis I, Lim CH, Takeo M, Cammer M, Taketo MM, Gay DL, Millar SE, Ito M
Nature 2023 616(7958):774-782

Bibliography

PubMed
PMID 37076619
DOI
10.1038/s41586-023-05960-6
Funding
Not fully stated in the available abstract.
Competing interests
Not stated in the available abstract.

Study snapshot

DesignIn vivo mouse mechanistic study (live imaging, single-cell RNA-seq, lineage tracing)
ModelMice
SampleNot applicable (animal mechanistic study)
InterventionNot applicable (observational/mechanistic, no intervention tested)
DurationLong-term lineage tracing across ageing
EndpointsMelanocyte stem cell mobility and state-switching; Accumulation of stranded, non-regenerating melanocyte stem cells with age

What the study showed, in plain terms

This mouse study found that the stem cells responsible for hair colour don't just sit passively in one state — they move back and forth between different maturity levels depending on their environment. With age, more of these stem cells get 'stuck' in a state where they no longer produce colour, which is proposed as a new explanation for why hair turns grey.

Key findings

Melanocyte stem cells (McSCs) toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature pigment-producing progeny, governed by local microenvironmental cues such as WNT signalling. The McSc system is maintained by reverted McSCs rather than by a reserved, unchanging stem cell pool. During ageing, stranded McSCs accumulate that no longer contribute to melanocyte regeneration, offering a new model for hair greying centred on stem cell mobility rather than simple stem cell loss.

What this study can and cannot tell us

Mouse mechanistic study; does not test fisetin, any flavonoid, or any human intervention. Establishes melanocyte stem cell mobility as relevant to hair greying but does not itself demonstrate a reversal treatment.

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Last verified

Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology