![]() ![]() Similar to HG epithelial cells, HG McSCs activate WNT signalling and undergo differentiation at the onset of regeneration 7. At the onset of the anagen growth phase, McSCs regenerate differentiated melanocytes that migrate downwards into the hair bulb, where they produce pigment for the hair. McSCs are located in the bulge and hair germ (HG) area in telogen-phase hair follicles (HFs) 4, 5, where they are surrounded by HF epithelial stem cells (bulge cells) 14 and progenitor cells (HG cells) 15, 16 that constitute to the McSC niche. The organization of the McSC system, responsible for hair pigmentation, is thought to parallel that of hair follicle stem cells (HFSCs) 5, 6, 7, 8. In this model, the life-long durability of self-renewing tissues is typically sustained by a functionally and molecularly heterogeneous pool of stem and progenitor cells. This theory proposes that stem cells (undifferentiated state) have two distinct fates: one to sustain themselves through self-renewal and the second to produce transit-amplifying (TA) progeny (intermediate differentiated state) that ultimately give rise to functional differentiated cells during tissue regeneration 12, 13, 14. Stem cell differentiation is generally viewed as unidirectional and follows the hierarchical model originally established through the study of haematopoietic stem cells 9, 10, 11. Mammalian tissue regeneration largely depends on the capacity of adult stem cells to differentiate. These results identify a new model whereby dedifferentiation is integral to homeostatic stem cell maintenance and suggest that modulating McSC mobility may represent a new approach for the prevention of hair greying. During ageing, there is accumulation of stranded McSCs that do not contribute to the regeneration of melanocyte progeny. Long-term lineage tracing demonstrated that the McSC system is maintained by reverted McSCs rather than by reserved stem cells inherently exempt from reversible changes. Live imaging and single-cell RNA sequencing revealed that McSCs are mobile, translocating between hair follicle stem cell and transit-amplifying compartments where they reversibly enter distinct differentiation states governed by local microenvironmental cues (for example, WNT). ![]() ![]() Here we show that most McSCs toggle between transit-amplifying and stem cell states for both self-renewal and generation of mature progeny, a mechanism fundamentally distinct from those of other self-renewing systems. Current dogma states that McSCs are reserved in an undifferentiated state in the hair follicle niche, physically segregated from differentiated progeny that migrate away following cues of regenerative stimuli 4, 5, 6, 7, 8. Other examples of NINDS funded research include using iPS cells to derive dopamine-producing neurons that might alleviate symptoms in patients with Parkinson’s disease, and using ES cells to generate cerebral organoids to model Zika virus infection.For unknow reasons, the melanocyte stem cell (McSC) system fails earlier than other adult stem cell populations 1, which leads to hair greying in most humans and mice 2, 3. NINDS supports a diverse array of research on stem cells, from studies of the basic biology of stem cells in the developing and adult mammalian brain, to studies focusing on nervous system disorders such as ALS or spinal cord injury. The promise of all stem cells for use in future therapies is exciting, but significant technical hurdles remain that will only be overcome through years of intensive research. For example, ES cells and iPS cells are able to differentiate into any type of cell, whereas adult stem cells are more restricted in their potential. While various types of stem cells share similar properties there are differences as well. There are multiple types of stem cell, such as embryonic stem (ES) cells, induced pluripotent stem (iPS) cells, and adult or somatic stem cells. Stem cells possess the unique ability to differentiate into many distinct cell types in the body, including brain cells, but they also retain the ability to produce more stem cells, a process termed self-renewal.
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