Thy-1(CD90) expression in dental pulp stem cells

Student thesis: Doctoral ThesisDoctor of Philosophy


The search for mesenchymal stem cells (MSCs) in adult tissues had led to the discovery of stem cells in many tissues in the body, including teeth. A better understanding of the biology of dental stem cell populations is a pre-requisite to allow their future use for clinical purposes.
To understand the biology of stem cell niches in the dental pulp, new genes expressed in dental tissues that could serve as markers of dental stem cells were investigated. The mouse incisor differs from mouse molars as well as human teeth in that it erupts continuously throughout the life of the animal. This continuous growth and eruption is related to the presence of the stem cells at the cervical end of the incisor to replace those lost from the incisor tip producing enamel and dentin of the erupting tooth.
From a mouse genome microarray using incisor body and cervical pulp cells, several genes were found to be up-regulated in the cervical area which has a MSC niche that provides a source of cells to replace those lost during continuous growth. Thy-1 (CD90) was selected as a stem cell marker to explore mesenchymal stem cell niches in murine dental pulp tissue. Protein expression was confirmed by flow cytometry and Thy-1 expression in cell culture was investigated. Its expression declined gradually with increasing cell passages. Whole mount in situ hybridization at different developmental stages showed that Thy-1 was selectively expressed in the cervical area of incisors, where
the MSC niche is located. In order to identify the function of this gene, genetic lineage tracing was used. Thy-1Cre expressing transgenic mice were crossed with Rosa26R reporter mice to follow the fates of Thy-1 expressing cells. Thy-1+ cells contributed to odontoblasts and pulp cells during incisor growth. However not all odontoblasts and pulp cells were Thy-1+ suggesting a complex MSC niche. Sonic Hedgehog (Shh) is the principle hedgehog gene in adult mouse incisors and cells responsive to it are stem cells inside the mouse incisor. Using transgenic mice where Shh signaling was modulated, Thy-1 expression was shown to be regulated in vivo by Shh in adult mouse incisor. Its expression was increased in Ptc-1fl/fl;CreERTm mice and was decreased in Polarisfl/fl;CreERTm mice. Therefore, Thy-1 is a marker for stem cell subpopulation in mouse incisor dental pulp and it is regulated by Shh.
Date of Award2012
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorPaul Sharpe (Supervisor) & Agamemnon Grigoriadis (Supervisor)

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