title: Papillary fibroblasts differentiate into reticular fibroblasts after prolonged in vitro culture.
abstract: The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high-passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high-passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti-skin-ageing strategies.
authors.affiliation: Department of Dermatology, Leiden University Medical Centre, Leiden, The Netherlands. d.g.janson@lumc.nl
authors.forename: David
authors.initials: D
authors.lastname: Janson
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Saintigny
authors.forename: Christian
authors.initials: C
authors.lastname: Mahé
authors.forename: Abdoelwaheb
authors.initials: A
authors.lastname: El Ghalbzouri
mesh_terms: D000199:Actins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D020405:Dermis / Q000166:cytology*; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D010641:Phenotype; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015595:Skin Aging; D013997:Time Factors; D011503:Transglutaminases / Q000378:metabolism; D000096985:Calponins; D000098853:Podoplanin
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D019204:GTP-Binding Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D000096985:Calponins; C541116:ACTA2 protein, human; C117468:PDPN protein, human; D000098853:Podoplanin