Miura Hirohito, Scott Jennifer K, Harada Shuitsu, Barlow Linda A
Department of Oral Physiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
Dev Dyn. 2014 Oct;243(10):1286-97. doi: 10.1002/dvdy.24121. Epub 2014 Mar 21.
Taste buds contain ∼60 elongate cells and several basal cells. Elongate cells comprise three functional taste cell types: I, glial cells; II, bitter/sweet/umami receptor cells; and III, sour detectors. Although taste cells are continuously renewed, lineage relationships among cell types are ill-defined. Basal cells have been proposed as taste bud stem cells, a subset of which express Sonic hedgehog (Shh). However, Shh+ basal cells turn over rapidly suggesting that Shh+ cells are post-mitotic precursors of some or all taste cell types.
To fate map Shh-expressing cells, mice carrying ShhCreER(T2) and a high (CAG-CAT-EGFP) or low (R26RLacZ) efficiency reporter allele were given tamoxifen to activate Cre in Shh+ cells. Using R26RLacZ, lineage-labeled cells occur singly within buds, supporting a post-mitotic state for Shh+ cells. Using either reporter, we show that Shh+ cells differentiate into all three taste cell types, in proportions reflecting cell type ratios in taste buds (I > II > III).
Shh+ cells are not stem cells, but are post-mitotic, immediate precursors of taste cells. Shh+ cells differentiate into each of the three taste cell types, and the choice of a specific taste cell fate is regulated to maintain the proper ratio within buds.
味蕾包含约60个细长细胞和几个基底细胞。细长细胞包括三种功能性味觉细胞类型:I型,神经胶质细胞;II型,苦/甜/鲜味受体细胞;III型,酸味感受器。尽管味觉细胞不断更新,但细胞类型之间的谱系关系尚不明确。基底细胞被认为是味蕾干细胞,其中一部分表达音猬因子(Shh)。然而,Shh+基底细胞更新迅速,这表明Shh+细胞是部分或所有味觉细胞类型的有丝分裂后前体细胞。
为了对表达Shh的细胞进行命运图谱分析,给携带ShhCreER(T2)和高效(CAG-CAT-EGFP)或低效(R26RLacZ)报告基因等位基因的小鼠注射他莫昔芬,以激活Shh+细胞中的Cre。使用R26RLacZ,谱系标记的细胞在味蕾中单个出现,支持Shh+细胞处于有丝分裂后状态。使用任何一种报告基因,我们都表明Shh+细胞分化为所有三种味觉细胞类型,其比例反映了味蕾中细胞类型的比例(I>II>III)。
Shh+细胞不是干细胞,而是有丝分裂后的味觉细胞直接前体细胞。Shh+细胞分化为三种味觉细胞类型中的每一种,并且特定味觉细胞命运的选择受到调控,以维持味蕾内的适当比例。