Merkel cells and touch domes: more than mechanosensory functions?

Xiao, Ying; Williams, Jonathan S.; Brownell, Isaac

doi:10.1111/exd.12456

Cited by 33 publications

(35 citation statements)

References 62 publications

(64 reference statements)

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“…Merkel cells of different shapes, including round or oval cells as well as dendritic cells, were noted in ESS in vivo (Fig 1). This is consistent with previous observations of Merkel cells in humans [26] and rodents [43–45]. KRT20 and KRT18 exhibited a perinuclear localization pattern in Merkel cells, although they were also localized to cellular projections in dendritic Merkel cells.…”

Section: Resultssupporting

confidence: 93%

“…Afferents expressing NF-H, which is reportedly found in more mature, myelinated neurons, were observed in the dermis of ESS at 4 weeks after grafting, but were not found in association with Merkel cells until 8 weeks after grafting. As previously observed in rodent and human skin [26, 43, 45], Merkel cells in ESS were heterogeneous in shape, displaying either a dendritic phenotype or more oval shape. It has been reported that in rodents, oval shaped Merkel cells tend to be innervated whereas dendritic cells may not be associated with nerves [43].…”

Section: Discussionsupporting

confidence: 67%

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

et al. 2019

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Engineered skin substitutes (ESS), prepared using primary human fibroblasts and keratinocytes with a biopolymer scaffold, were shown to provide stable closure of excised burns, but relatively little is known about innervation of ESS after grafting. This study investigated innervation of ESS and, specifically, whether Merkel cells are present in healed grafts. Merkel cells are specialized neuroendocrine cells required for fine touch sensation in skin. We discovered cells positive for keratin 20 (KRT20), a general marker for Merkel cells, in the basal epidermis of ESS after transplantation to mice, suggesting the presence of Merkel cells. Cells expressing KRT20 were not observed in ESS in vitro . However, widely separated KRT20-positive cells were observed in basal epidermis of ESS by 2 weeks after grafting. By 4 weeks, these cells increased in number and expressed keratins 18 and 19, additional Merkel cells markers. Putative Merkel cell numbers increased further between weeks 6 and 14; their densities varied widely and no specific pattern of organization was observed, similar to Merkel cell localization in human skin. KRT20-positive cells co-expressed epidermal markers E-cadherin and keratin 15, suggesting derivation from the epidermal lineage, and neuroendocrine markers synaptophysin and chromogranin A, consistent with their identification as Merkel cells. By 4 weeks after grafting, some Merkel cells in engineered skin were associated with immature afferents expressing neurofilament-medium. By 8 weeks, Merkel cells were complexed with more mature neurons expressing neurofilament-heavy. Positive staining for human leukocyte antigen demonstrated that the Merkel cells in ESS were derived from grafted human cells. The results identify, for the first time, Merkel cell-neurite complexes in engineered skin in vivo . This suggests that fine touch sensation may be restored in ESS after grafting, although this must be confirmed with future functional studies.

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 67%

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

et al. 2019

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“…This is a novel response that we hypothesize is secondary to mild superficial wound healing. We confirmed that these new Merkel cells arise from touch dome keratinocytes, as has been previously reported (Doucet et al, 2013; Xiao et al, 2014). …”

Section: Discussionsupporting

confidence: 92%

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

Wright

Logan

Bolock

et al. 2017

Developmental Biology

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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.

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“…Quantitative increase of MCs in psoriatic lesional skin signifies its role in cutaneous immunology. [ 53 ]…”

Section: Functionsmentioning

confidence: 99%