Quiescent adult stem cells in murine teeth are regulated by Shh signaling
Quiescent adult stem cells in murine teeth are regulated by Shh signaling
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DOI：
10.1007/s00441-017-2632-x
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发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Ohshima, Hayato
中科院分区：
文献类型：
--
作者：
Ishikawa, Yuko;Nakatomi, Mitsushiro;Ohshima, Hayato
调节牙齿中静止成体干细胞维持的机制仍有待充分阐明。我们的目的是澄清BrdU标记保留细胞（LRC）和音刺猬（Shh）信号在小鼠牙齿之间的关系。出生前BrdU标记后，在出生后第1天（P1）至第5周（P5 W）期间分析小鼠幼崽。石蜡切片进行BrdU、Sox 2、Gli 1、Shh、Patched 1（Ptch 1）和Ki 67的免疫组织化学处理，并进行Shh和Ptch 1的原位杂交。LRC、Gli 1-（+）细胞和Ptch 1-（+）细胞共定位于切牙根尖芽和根尖牙乳头的外釉上皮。在磨牙的发育过程中，致密的LRC在P1时数量众多，但在牙发育过程中数量减少，并保持在牙髓组织的中心。Gli 1-（+）细胞在实验期主要分布于髓角，而在P2- 5 W，Gli 1-（+）细胞数量增多，主要分布于髓中心。PTCH 1-（+）细胞在P1时定位于髓角，P3 W后在髓中心数量增多。Shh mRNA首先在釉质上皮表达，然后转移到成牙本质细胞和其他牙髓细胞。Shh蛋白分布于切牙和磨牙的上皮和间充质组织中。这些研究结果表明，静止的牙齿干细胞的Shh信号的调节，和Shh信号起着至关重要的作用，在成牙本质细胞的分化和完整性在上皮间充质相互作用和牙本质形成。
The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors. In developing molars, dense LRCs were numerous at P1 but then decreased in number over the course of odontogenesis and were maintained in the center of pulp tissue. Gli1-(+) cells were maintained in the pulp horn during the examined stages, while they increased in number and were maintained in the center of pulp tissue during P2-5W. Ptch1-(+) cells were localized in the pulp horn at P1 and increased in number in the center of the pulp after P3W. Shh mRNA was first expressed in the enamel epithelium and then shifted to odontoblasts and other pulp cells. Shh protein was distributed in the epithelial and mesenchymal tissues of incisors and molars. These findings suggest that quiescent dental stem cells are regulated by Shh signaling, and that Shh signaling plays a crucial role in the differentiation and integrity of odontoblasts during epithelial-mesenchymal interactions and dentinogenesis.