Sensory Nerve Sprouting into Human Skin Explants Confers Improved Survival to Merkel Cells Independent of Merkel Cell-Neurite Complexes.

Merkel cells (MCs) are required for gentle touch responses ( Maksimovic et al., 2014 Maksimovic S. Nakatani M. Baba Y. Nelson A.M. Marshall K.L. Wellnitz S.A. et al. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature. 2014; 509: 617-621 Crossref PubMed Scopus (341) Google Scholar ; Maricich et al., 2009 Maricich S.M. Wellnitz S.A. Nelson A.M. Lesniak D.R. Gerling G.J. Lumpkin E.A. et al. Merkel cells are essential for light-touch responses. Science. 2009; 324: 1580-1582 Crossref PubMed Scopus (211) Google Scholar ) and have been recently shown to be involved in abnormal sensations such as alloknesis and allodynia ( Feng et al., 2018 Feng J. Luo J. Yang P. Du J. Kim B.S. Hu H. Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch. Science. 2018; 360: 530-533 Crossref PubMed Scopus (104) Google Scholar , Feng et al., 2022 Feng J. Zhao Y. Xie Z. Zang K. Sviben S. Hu X. et al. 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Merkel cells are long-lived cells whose production is stimulated by skin injury. Dev Biol. 2017; 422: 4-13 Crossref PubMed Scopus (12) Google Scholar ), and descend from the epidermal lineage ( Tilling et al., 2014 Tilling T. Wladykowski E. Failla A.V. Houdek P. Brandner J.M. Moll I. Immunohistochemical analyses point to epidermal origin of human Merkel cells. Histochem Cell Biol. 2014; 141: 407-421 Crossref PubMed Scopus (21) Google Scholar ; Woo et al., 2010 Woo S.H. Stumpfova M. Jensen U.B. Lumpkin E.A. Owens D.M. Identification of epidermal progenitors for the Merkel cell lineage. Development. 2010; 137: 3965-3971 Crossref PubMed Scopus (63) Google Scholar ), it is not yet fully understood how MCs are lost during aging, whether they decrease as MC-neurite complexes and/or independently from each other ( Fundin et al., 1997 Fundin B.T. Bergman E. Ulfhake B. Alterations in mystacial pad innervation in the aged rat. 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Therefore, we aimed to clarify whether MCs in human skin need direct support from connecting nerve fibers or can survive alone by taking advantage of our recently published technique of denervated human skin explants into which human sensory nerves sprout( Chéret et al., 2022 Chéret J. Piccini I. Gherardini J. Ponce L. Bertolini M. Paus R. Sensory reinnervation of human skin by human neural stem cell‒derived peripheral neurons ex vivo. J Invest Dermatol. 2022; 142: 257-261.e5 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ).