Hair graying is a common phenomenon observed in most humans and rodents, often reflecting premature aging of melanocyte stem cells (McSCs) compared to other mature stem cell populations. A recent study showed that, contrary to popular belief, McSCs do not remain in an undifferentiated state within their follicular structure, but fluctuate between stem cell states and in-transit amplifying cell (AT) states for their self-renewal and production. Progeny This finding suggests a fundamentally different model of melanocyte stem cell maintenance, where differentiation plays a key role.
Motility and plasticity of McSCs
Through live imaging and single-cell RNA sequencing, it was revealed that McSCs are mobile, moving between follicular stem cell compartments and TA compartments where they can reversibly enter different differentiation states. These states are governed by local microenvironmental cues, such as WNT. Long-term lineage tracing showed that the McSC system is maintained by reverted McSCs rather than reverted stem cells, which are immune to irreversible changes.
McSCs and hair pigmentation
In contrast to traditional hierarchical models of stem cell differentiation, which suggest a unidirectional process, this study suggests that most McSCs can alternate between transit-amplifying and stem cell states. This ability to switch between different states allows not only the self-renewal of McSCs but also the production of mature melanocyte progeny necessary for hair pigmentation.
A possible approach to hair whitening
The accumulation of “failed” McSCs that do not contribute to the regeneration of melanocyte progeny during senescence indicates a specific vulnerability in the long-term maintenance of McSCs. Modulating the dynamics of McSCs may present a new strategy for the prevention of hair graying, providing promising insights for future research in the field of tissue regeneration and treatment of visible signs of aging.
Revelations on Evolution: How Dinosaurs Shaped Our Aging!
Implications and future perspectives
The discovery that differentiation is integral to the homeostatic maintenance of stem cells opens new avenues of research to understand stem cell specific dynamics in other tissue systems. Furthermore, understanding the mechanism of reversibility of McSC may inform the development of novel therapies for gray hair recovery and potentially influence treatment approaches against various types of cancer, such as melanoma, which exhibit a similar retention capacity of self. – Renewal despite wide variation.
This study represents a turning point in our understanding of the biology of melanocyte stem cells, highlighting the importance of cellular plasticity in tissue maintenance and providing new perspectives for treating pigmentary disorders and preventing hair aging.
Source de l'étude : Sun, Q., Lee, W., Hu, H. et al. Dedifferentiation maintains melanocyte stem cells in a dynamic niche. Nature 616, 774–782 (2023). https://doi.org/10.1038/s41586-023-05960-6
