Progenitor cells expressing nestin, a neural crest stem cell marker, differentiate into outer root sheath keratinocytes
Progenitor cells expressing nestin, a neural crest stem cell marker, differentiate into outer root sheath keratinocytes
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DOI：
10.1111/vde.12771
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发表时间：
2019-07-12
影响因子：
1.4
通讯作者：
Nishifuji, Koji
中科院分区：
文献类型：
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作者：
Onishi, Saki;Baba, Yuta;Nishifuji, Koji
背景Nestin最初被描述为神经嵴干细胞标记物，已知其在人、犬和小鼠毛发生长期的隆突毛囊细胞中表达。然而，表达巢蛋白的细胞分化成毛囊或表皮成分的能力还没有得到充分的研究。假设/目的为了确定表达巢蛋白的细胞是否能够分化为角质形成细胞。动物/材料双转基因小鼠系Nes-Cre/CAG-CAT-EGFP，其中增强型绿色荧光蛋白（EGFP）在巢蛋白启动子驱动的基于Cre的重组中表达。方法：用免疫荧光和免疫组织化学方法分析EGFP（+）和nestin（+）细胞在小鼠皮肤中的组织分布。结果EGFP（+）细胞主要分布于生长期和休止期毛囊的外表皮细胞层，而在毛囊间的表皮细胞中很少见到。毛囊外层的EGFP（+）细胞共表达角蛋白14，一种外根鞘（ORS）角质形成细胞的标记物，但不表达透明质颗粒，一种内根鞘角质形成细胞的标记物。巢蛋白的免疫染色未能检测到其在大多数毛囊上皮细胞中的表达，这表明ORS中的EGFP（+）细胞来源于表达巢蛋白的祖细胞，这些祖细胞已经沿着上皮细胞谱系进一步定型，其中巢蛋白不再表达。结论和临床意义-这些结果表明，分化成ORS角质形成细胞的祖细胞是不同于其他毛囊或表皮成分，并提供再生医学和毛囊肿瘤的分子分类的影响。
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.