Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis

Investigations into stem cell-fueled renewal of an organ benefit from an inventory of cell type-specific markers and a deep understanding of the cellular diversity within stem cell niches. Using the adult mouse incisor as a model for a continuously renewing organ, we performed an unbiased analysis of gene co-expression relationships to identify modules of co-expressed genes that represent differentiated cells, transit-amplifying cells, and residents of stem cell niches. Through in vivo lineage tracing, we demonstrated the power of this approach by showing that co-expression module members Lrig1 and Igfbp5 define populations of incisor epithelial and mesenchymal stem cells. We further discovered that two adjacent mesenchymal tissues, the periodontium and dental pulp, are maintained by distinct pools of stem cells. These findings reveal novel mechanisms of incisor renewal and illustrate how gene co-expression analysis of intact biological systems can provide insights into the transcriptional basis of cellular identity. DOI: http://dx.doi.org/10.7554/eLife.24712.001
eLife digest To maintain healthy tissues and organs in adult animals, the cells that die or become damaged need to be replaced. This process is made possible by adult stem cells, which can divide to produce more stem cells (via a process called self-renewal) or specialize into other types of cells. This means that stem cells can maintain their own population by self-renewal while continually being able to generate specialized cells that replenish tissues and organs. Mouse incisor teeth are useful models to understand how adult organs are regenerated because, unlike human teeth, the incisor teeth of mice and other rodents grow continuously throughout the life of the animal. The tip of the mouse incisor is eroded as the animal eats, resulting in the loss of cells. A group of adult stem cells at the base of the tooth produce new cells that then move to the tip to replace the lost cells. Although virtually all cells in the body have the same set of genes, only small subsets are active in each cell type. It is possible to distinguish cells of different types by their patterns of gene activity. However, little is known about the gene expression patterns that distinguish stem cells and specialized cells in mouse incisors. Using a technique called gene co-expression analysis, Seidel et al. set out to identify all the genes that are active in stem cells and their descendants at the base of the mouse incisor. The experiments reveal the patterns of activity of thousands of genes, providing a clearer picture of the different cell types present and the biological processes at play. Seidel et al. then used other techniques to identify two genes that can be used as markers to identify distinct types of stem cells in the incisor. The next steps following on from this work will be to understand in more detail how stem cells behave in renewing the incisor. In the future, these findings may help guide the use of stem cells in regenerating human teeth and other organs. DOI: http://dx.doi.org/10.7554/eLife.24712.002