A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors

Abstract

The extent to which heterogeneity within mesenchymal stem cell (MSC) populations is related to function is not understood. Using the archetypal MSC in vitro surface marker, CD90/Thy1, here we show that 30% of the MSCs in the continuously growing mouse incisor express CD90/Thy1 and these cells give rise to 30% of the differentiated cell progeny during postnatal development. In adulthood, when growth rate homeostasis is established, the CD90/Thy1+ MSCs decrease dramatically in number. When adult incisors are cut, the growth rate increases to rapidly re-establish tooth length and homeostasis. This accelerated growth rate correlates with the re-appearance of CD90/Thy+ MSCs and re-establishment of their contribution to cell differentiation. A population of Celsr1+ quiescent cells becomes mitotic following clipping and replenishes the CD90/Thy1 population. A sub-population of MSCs thus exists in the mouse incisor, distinguished by expression of CD90/Thy1 that plays a specific role only during periods of increased growth rate.

Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications

“…However, as revealed by An et al, CD90 + cells account for 30% of incisor MSCs which contribute to 30% of pulp cells and odontoblasts during early postnatal development. 14…”

“…It is well known that most MSCs express CD90 in vitro, as aforementioned. However, as revealed by An et al, CD90 + cells account for 30% of incisor MSCs which contribute to 30% of pulp cells and odontoblasts during early postnatal development . Once incisor growth homeostasis has been established after eruption in adult, CD90 + MSCs decrease substantially by twofold as compared to postnatal incisor, and the population of CD90 + MSCs which give rise to differentiation is approximately depleted and becomes nearly undetectable.…”

“…Notably, the majority of Gli1 + cells in mouse incisor do not express classic in vitro markers of MSCs, including CD44, CD73, CD105, CD146, and nestin, indicating that classic MSC markers may not be efficient to confirm MSCs in vivo. Moreover, Celsr1, a marker known from hematopoietic stem cells, is identified to label a rare and quiescent subpopulation of MSCs in mouse incisor pulp . Celsr1 + cells do not express CD90 under homeostasis.…”

Tissue Mechanical Forces and Evolutionary Developmental Changes Act Through Space and Time to Shape Tooth Morphology and Function

“…This notion is consistent with recent findings that SHH‐secreting neurovascular bundles maintain dental mesenchymal homeostasis, but these bundles may also provide mechanical loading through musculature to regulate stem cells. The observation that a subset of dental mesenchymal stem cells increase their rate of proliferation (and thus the rate of tooth eruption) after rodent incisors are cut prompted hypotheses that changes in the mechanical forces experienced by the clipped teeth through loss of occlusion were responsible . However, reducing mechanical force from occlusion by clipping only one incisor produced no observed difference in growth rates, suggesting that loss of occlusion force was not sufficient to alter growth rates in mesenchymal cells .…”

“…The observation that a subset of dental mesenchymal stem cells increase their rate of proliferation (and thus the rate of tooth eruption) after rodent incisors are cut prompted hypotheses that changes in the mechanical forces experienced by the clipped teeth through loss of occlusion were responsible . However, reducing mechanical force from occlusion by clipping only one incisor produced no observed difference in growth rates, suggesting that loss of occlusion force was not sufficient to alter growth rates in mesenchymal cells . Nonetheless, previous research has shown that molecular mechanisms of tooth eruption in ever‐growing teeth may differ from those of teeth with finite growth .…”