Merkel cells are long-lived cells whose production is stimulated by skin injury

Abstract

Mechanosensitive Merkel cells are thought to have finite lifespans, but controversy surrounds the frequency of their replacement and which precursor cells maintain the population. We found by embryonic EdU administration that Merkel cells undergo terminal cell division in late embryogenesis and survive long into adulthood. We also found that new Merkel cells are produced infrequently during normal skin homeostasis and that their numbers do not change during natural or induced hair cycles. In contrast, live imaging and EdU experiments showed that mild mechanical injury produced by skin shaving dramatically increases Merkel cell production. We confirmed with genetic cell ablation and fate-mapping experiments that new touch dome Merkel cells in adult mice arise from touch dome keratinocytes. Together, these independent lines of evidence show that Merkel cells in adult mice are long-lived, are replaced rarely during normal adult skin homeostasis, and that their production can be induced by repeated shaving. These results have profound implications for understanding sensory neurobiology and human diseases such as Merkel cell carcinoma.

Identification of Merkel cells associated with neurons in engineered skin substitutes after grafting to full thickness wounds

“…Thus, it was suggested that Merkel cells in human skin might be renewed from a population of undifferentiated keratinocytes or common progenitor cells [55]. Labeling experiments in mice have shown that Merkel cells are long-lived cells that are produced very rarely in adult skin under homeostatic conditions [56]. However, upon mild skin injury, increased numbers of Merkel cells were produced, and fate-mapping showed that their differentiation was induced from touch dome keratinocytes [56].…”

A novel player in the field: Merkel disc in touch, itch and pain

“…Moreover, touch domes were reported to undergo a rapid remodelling and the number of Merkel cells per touch dome oscillated within hair cycles until adulthood . On the other hand, other studies showed that embryonic‐derived Merkel cells survived for at least 9 months and the average number of Merkel cells per touch dome remained steady in both natural and induced hair circles . Moreover, it is also possible that changes in number of Merkel cells under normal development and pathological conditions such as skin inflammation might have distinct effects on sensory biology.…”

Intracellular DNA replication and differentiation of Trypanosoma cruzi is asynchronous within individual host cells in vivo at all stages of infection

“…EdU distribution in murine tissues is extensive and incorporation is stable. For example, Merkel cells from mice whose PLOS NEGLECTED TROPICAL DISEASES mothers were injected with EdU during pregnancy remain labelled nine months after birth, suggesting that the analogue is not removed during DNA repair [30][31][32]. Labelling of replicating host cells within a given tissue section can therefore be used as an internal control for EdU tissue penetration to sites of T. cruzi infection.…”