Abstract

The mouse incisor is a valuable but under-utilized model organ for studying the behavior of adult stem cells. This remarkable tooth grows continuously throughout the animal's lifetime and houses two distinct epithelial stem cell niches called the labial and lingual cervical loop (laCL and liCL, respectively). These stem cells produce progeny that undergo a series of well-defined differentiation events en route to becoming enamel-producing ameloblasts. During this differentiation process, the progeny move out of the stem cell niche and migrate toward the distal tip of the tooth. Although the molecular pathways involved in tooth development are well documented, little is known about the roles of miRNAs in this process. We used microarray technology to compare the expression of miRNAs in three regions of the adult mouse incisor: the laCL, liCL, and ameloblasts. We identified 26 and 35 differentially expressed miRNAs from laCL/liCL and laCL/ameloblast comparisons, respectively. Out of 10 miRNAs selected for validation by qPCR, all transcripts were confirmed to be differentially expressed. In situ hybridization and target prediction analyses further supported the reliability of our microarray results. These studies point to miRNAs that likely play a role in the renewal and differentiation of adult stem cells during stem cell-fueled incisor growth.

Highlights

  • Enamel, the outermost layer of teeth and the hardest substance in the mammalian body, is generated by specialized, epithelialderived cells called ameloblasts

  • By comparing three specific regions in the adult mouse incisor, we have identified miRNAs that may play a role in the self-renewal and differentiation of stem cells

  • Specific molecular pathways involved in tooth development have been well documented, little is known regarding the role of miRNAs in this process

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Summary

Introduction

The outermost layer of teeth and the hardest substance in the mammalian body, is generated by specialized, epithelialderived cells called ameloblasts. Humans possess a limited ability to regenerate enamel due to the loss of ameloblasts upon tooth eruption and the absence of an ameloblast stem cell population. Some mammals have teeth that grow continuously throughout life. This growth is made possible by the presence of epithelial and mesenchymal stem cells that have the capacity to self-renew and differentiate into ameloblasts and dentin-forming odontoblasts [1]. One such case is the adult mouse incisor, which provides a valuable system for studying the molecular and cellular pathways that govern stem cell self-renewal and differentiation

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