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

Abstract

Background -Nestin, which was originally described as a neural crest stem cell marker, is known to be expressed in bulge follicle cells of human, canine and murine anagen hairs. However, the capacity of nestin-expressing cells to differentiate into the components of the hair follicle or the epidermis has been insufficiently investigated.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.

Desmoplastic fibroma of the jaw bones: A series of twenty-two cases

“…Therefore, bone lesions may display unique histological changes in the jawbones. Craniofacial bone development is different from long bones and that it develops from neural crest [27] , [13] , [10] , [28] , [29] . This difference may also be effective in immunostaining results.…”

“…Nestin is a class VI intermediate filament protein; it is known as a specific marker of neural or neural crest stem cells [10] , [13] , [27] , [28] , [29] . Nestin, which tends to be more strongly expressed in mandibular bone morphogenetic stem cells (R).…”

“…On the other hand, craniofacial bone development is different from long bones and that it develops from the neural crest [10] , [11] , [12] , [13] . Clinical and radiologic appearances of the jaw bone DF are nonspecific and they can mimic several other common lesions including odontogenic tumors.…”

Nestin as a marker of unipotent epithelial progenitor cells differentiate into outer root sheath keratinocytes in embryonic and adult hair follicles

“…The Nes-Cre/CAG-CAT-EGFP mouse line [24] was generated by crossing CAG-CAT-EGFP mice (courtesy of Junichi Miyazaki, Osaka University, Japan), in which the chloramphenicol acetyltransferase (CAT) gene is anked by two loxP sites [14], with Nes-Cre mice (courtesy of Ryoichiro Kageyama, Kyoto University, Japan) [9]; both mouse strains have a C57BL/6 background. The Nes-CreERT2/CAG-CAT-EGFP mouse line was generated by crossing CAG-CAT-EGFP mice with Nes-CreERT2 mice (courtesies of Itaru Imayoshi and Ryoichiro Kageyama, Kyoto University, Japan), which harbor the CreERT2 gene downstream of the nestin promoter and also have a C57BL/6 background.…”

“…Moreover, studies using nestin-driven green uorescent protein (ND-GFP) transgenic mice revealed that ND-GFP cells in the upper HF are multipotent, as they can differentiate into cell lineages with characteristics of neural cells, glial cells, muscle cells, melanocytes, and keratinocytes in vitro [2][3][4][5]18]. Previously, we reported that ORS keratinocytes of adult mice are the descendants of nestin-expressing cells, despite being an epithelial cell lineage [24]. This study aimed to de ne the exact stage when nestin-expression ORS stem/precursor cells appear during HF morphogenesis.…”