Department of Orofacial Sciences, Program in Craniofacial and Mesenchymal Biology, UCSF, 513 Parnassus Avenue, San Francisco, CA 94143-0442, USA.
Development. 2010 Nov;137(22):3753-61. doi: 10.1242/dev.056358.
In many organ systems such as the skin, gastrointestinal tract and hematopoietic system, homeostasis is dependent on the continuous generation of differentiated progeny from stem cells. The rodent incisor, unlike human teeth, grows throughout the life of the animal and provides a prime example of an organ that rapidly deteriorates if newly differentiated cells cease to form from adult stem cells. Hedgehog (Hh) signaling has been proposed to regulate self-renewal, survival, proliferation and/or differentiation of stem cells in several systems, but to date there is little evidence supporting a role for Hh signaling in adult stem cells. We used in vivo genetic lineage tracing to identify Hh-responsive stem cells in the mouse incisor and we show that sonic hedgehog (SHH), which is produced by the differentiating progeny of the stem cells, signals to several regions of the incisor. Using a hedgehog pathway inhibitor (HPI), we demonstrate that Hh signaling is not required for stem cell survival but is essential for the generation of ameloblasts, one of the major differentiated cell types in the tooth, from the stem cells. These results therefore reveal the existence of a positive-feedback loop in which differentiating progeny produce the signal that in turn allows them to be generated from stem cells.
在许多器官系统中，如皮肤、胃肠道和造血系统，内稳态依赖于干细胞不断产生分化后代。与人类牙齿不同，啮齿动物的门牙在动物的整个生命周期中都在生长，这为一个器官提供了一个很好的例子，如果新分化的细胞不再从成体干细胞形成，该器官会迅速恶化。Hedgehog (Hh) 信号已被提议调节几个系统中的干细胞的自我更新、存活、增殖和/或分化，但迄今为止，几乎没有证据支持 Hh 信号在成体干细胞中的作用。我们使用体内遗传谱系追踪来鉴定小鼠门牙中的 Hh 反应性干细胞，并表明由干细胞的分化后代产生的 sonic hedgehog (SHH) 信号传递到门牙的几个区域。使用 Hedgehog 途径抑制剂 (HPI)，我们证明 Hh 信号对于干细胞的存活不是必需的，但对于从干细胞产生成釉细胞（牙齿的主要分化细胞类型之一）是必需的。因此，这些结果揭示了一个正反馈回路的存在，其中分化后代产生信号，反过来又允许它们从干细胞中产生。
