Lgr5 Marks Neural Crest Derived Multipotent Oral Stromal Stem Cells
Lgr5 Marks Neural Crest Derived Multipotent Oral Stromal Stem Cells
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DOI：
10.1002/stem.2314
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发表时间：
2016-03-01
期刊：
影响因子：
5.2
通讯作者：
Kobielak, Agnieszka
中科院分区：
文献类型：
--
作者：
Boddupally, Keerthi;Wang, Guangfang;Kobielak, Agnieszka
研究表明，具有神经嵴（NC）起源的多能干细胞在口腔粘膜中持续存在至成年。然而，它们在正常体内平衡中的确切定位和作用是未知的。在这项研究中，我们发现Lgr5在胚胎发育过程中在NC细胞中表达，从而产生成年舌和口腔粘膜中的休眠干细胞。这些Lgr5阳性口腔基质干细胞显示NC干细胞的特性，包括克隆生长和多能分化。RNA测序显示，成人Lgr5+口腔基质干细胞表达大量的神经嵴相关标志物，如Sox 9，Twist 1，Snai 1，Myc，Ets 1，Crapp 1，Epha2和Itgb 1。使用谱系追踪实验，我们表明，这些细胞持续一年以上的腹侧舌和口腔粘膜的某些地区，并产生基质后代。在体内移植证明，这些细胞重建基质。我们的研究首次表明，Lgr 5在胚胎9.5天（E9.5）的NC细胞中表达，并在胚胎发育过程中和出生后在舌腹侧的基质中维持，以及口腔粘膜的某些区域，并且Lgr 5+细胞参与基质的维持。
It has been suggested that multipotent stem cells with neural crest (NC) origin persist into adulthood in oral mucosa. However their exact localization and role in normal homeostasis is unknown. In this study, we discovered that Lgr5 is expressed in NC cells during embryonic development, which give rise to the dormant stem cells in the adult tongue and oral mucosa. Those Lgr5 positive oral stromal stem cells display properties of NC stem cells including clonal growth and multipotent differentiation. RNA sequencing revealed that adult Lgr5+ oral stromal stem cells express high number of neural crest related markers like Sox9, Twist1, Snai1, Myc, Ets1, Crabp1, Epha2, and Itgb1. Using lineage-tracing experiments, we show that these cells persist more than a year in the ventral tongue and some areas of the oral mucosa and give rise to stromal progeny. In vivo transplantation demonstrated that these cells reconstitute the stroma. Our studies show for the first time that Lgr5 is expressed in the NC cells at embryonic day 9.5 (E9.5) and is maintained during embryonic development and postnataly in the stroma of the ventral tongue, and some areas of the oral mucosa and that Lgr5+ cells participate in the maintenance of the stroma.