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Immunohistochemical analyses point to epidermal origin of human Merkel cells

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Abstract

Merkel cells, the neurosecretory cells of skin, are essential for light-touch responses and may probably fulfill additional functions. Whether these cells derive from an epidermal or a neural lineage has been a matter of dispute for a long time. In mice, recent studies have clearly demonstrated an epidermal origin of Merkel cells. Given the differences in Merkel cell distribution between human and murine skin, it is, however, unclear whether the same holds true for human Merkel cells. We therefore attempted to gain insight into the human Merkel cell lineage by co-immunodetection of the Merkel cell marker protein cytokeratin 20 (CK20) with various proteins known to be expressed either in epidermal or in neural stem cells of the skin. Neither Sox10 nor Pax3, both established markers of the neural crest lineage, exhibited any cell co-labeling with CK20. By contrast, β1 integrin, known to be enriched in epidermal stem cells, was found in nearly 70 % of interfollicular epidermal and 25 % of follicular Merkel cells. Moreover, LRIG1, also enriched in epidermal stem cells, displayed significant co-immunolabeling with CK20 as well (approximately 20 % in the interfollicular epidermis and 7 % in the hair follicle, respectively). Further epidermal markers were detected in sporadic Merkel cells. Cells co-expressing CK20 with epidermal markers may represent a transitory state between stem cells and differentiated cells. β1 integrin is probably also synthesized by a large subset of mature Merkel cells. Summarizing, our data suggest that human Merkel cells may originate from epidermal rather than neural progenitors.

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Acknowledgments

We thank Prof. Satoshi Itami (Osaka) for kindly providing anti-LRIG1 antibodies. The Pax3 monoclonal antibody, developed by C.P. Ordahl, as well as the P5D2 monoclonal antibody against β1 integrin, developed by E.A. Wayner, were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Sciences, Iowa City, IA 52242. We would also like to thank Dr. Sandra Medic (Perth, Australia) for helpful advice on Pax3 immunostainings.

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  1. Department of Dermatology and Venerology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Thomas Tilling, Ewa Wladykowski, Pia Houdek, Johanna M. Brandner & Ingrid Moll

  2. UKE Microscopy Imaging Facility (UMIF), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Antonio Virgilio Failla

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  1. Thomas Tilling
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Correspondence to Thomas Tilling.

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Tilling, T., Wladykowski, E., Failla, A.V. et al. Immunohistochemical analyses point to epidermal origin of human Merkel cells. Histochem Cell Biol 141, 407–421 (2014). https://doi.org/10.1007/s00418-013-1168-8

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