Progenitor cells expressing nestin, a neural crest stem cell marker, differentiate into outer root sheath keratinocytes

CONTEXTE: La nestine, qui a ete initialement decrite comme un marqueur des cellules souches des cretes neurales, est connue pour etre exprimee par les cellules folliculaires du bulge des poils anagenes chez l'homme, le chien et la souris. Cependant, la capacite des cellules a exprimer la nestine pour differencier les differents composants du follicule pileux ou de l’epiderme a ete insuffisamment etudiee. HYPOTHESES/OBJECTIFS: Determiner si les cellules exprimant la nestine sont capables de se differencier en keratinocytes. SUJETS/MATERIELS: Une lignee de souris double-transgenique Nes-Cre/CAG-CAT-EGFP, pour laquelle une augmentation de proteine fluorescente verte (EGFP) s'exprime sur la recombinaison Cre-based due au prompteur de nestine. MATERIEL ET METHODE: La distribution tissulaire des cellules EGFP+ et nestine+ dans la peau de souris a ete analysee par immunofluorescence et immunohistochimie. RESULTATS: Les cellules EGFP+ ont ete reconnues dans les couches cellulaires epitheliales externes des follicules pileux anagenes et telogenes mais ont ete rarement vus dans l’epiderme interfolliculaire. Les cellules EGFP+ des couches externes des follicules pileux co-exprimaient keratine 14, un marqueur des keratinocytes de ORS (outer root sheath) mais pas de granules de trichohyaline, un marqueur cellulaire des keratinocytes de la gaine epitheliale interne. L'immunomarquage pour la nestine n’ a pas permis de detecter son expression dans la majorite des cellules epitheliales des follicules pileux, suggerant que les cellules EGFP+ de l'ORS etaient derivees des cellules pro-genitrices exprimant la nestine qui se sont engagees dans la lignee cellulaire epitheliale, ou la nestine n'est plus exprimee. HYPOTHESIS/OBJECTIVES: To determine whether nestin-expressing cells are capable of differentiating into keratinocytes. ANIMALS/MATERIALS: A double-transgenic mouse line Nes-Cre/CAG-CAT-EGFP, in which enhanced green fluorescent protein (EGFP) is expressed upon Cre-based recombination driven by the nestin promoter. METHODS AND MATERIALS: The tissue distribution of EGFP+ and nestin+ cells in the skin of the mouse line was analysed by immunofluorescence and immunohistochemical analyses. RESULTS: EGFP+ cells were recognized in the outer epithelial cell layers of anagen and telogen hair follicles, but rarely seen in the interfollicular epidermis. The EGFP+ cells in the outer layers of the hair follicles coexpressed keratin 14, a marker of the outer root sheath (ORS) keratinocytes, but not trichohyalin granules, an inner root sheath keratinocyte cell marker. Immunostaining for nestin failed to detect its expression in the majority of hair follicle epithelial cells, suggesting that the EGFP+ cells in the ORS were derived from nestin-expressing progenitor cells that had become further committed along the epithelial cell lineage, where nestin is no longer expressed. CONCLUSIONS AND CLINICAL IMPORTANCE: These results suggest that progenitor cells that differentiate into ORS keratinocytes are distinct from those for other hair follicle or epidermal components and provide implications for regenerative medicine and the molecular classification of hair follicle tumours.