title: 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.
authors.affiliation: Center for Neurosciences, University of Pittsburgh, Pittsburgh, PA 15260, United States. Electronic address: mcw47@pitt.edu.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Wright
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15260, United States.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Logan
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224, United States.
authors.forename: Alexa M
authors.initials: AM
authors.lastname: Bolock
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224, United States.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Kubicki
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224, United States.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Hemphill
authors.affiliation: Division of Neonatology, Department of Pediatrics, US Benioff Children's Hospital, University of California San Francisco, San Francisco, CA 94143, United States.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Sanders
authors.affiliation: Richard King Mellon Institute for Pediatric Research, Department of Pediatrics, University of Pittsburgh and Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA 15224, United States. Electronic address: stephen.maricich@bmrn.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Maricich
mesh_terms: D000818:Animals; D015266:Carcinoma, Merkel Cell / Q000209:etiology; D049109:Cell Proliferation; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins; D006706:Homeostasis; D018862:Merkel Cells / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000166:cytology*
chemical_list: D049452:Green Fluorescent Proteins; C031086:5-ethynyl-2'-deoxyuridine; D003857:Deoxyuridine
keywords: Development; Merkel cell carcinoma; Somatosensation; Touch