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Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation
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Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation
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Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation
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Journal Article
Single-cell RNA-seq analysis of rat molars reveals cell identity and driver genes associated with dental mesenchymal cell differentiation
2024
Overview
Background
The molecular mechanisms and signaling pathways involved in tooth morphogenesis have been the research focus in the fields of tooth and bone development. However, the cell population in molars at the late bell stage and the mechanisms of hard tissue formation and mineralization remain limited knowledge.
Results
Here, we used the rat mandibular first and second molars as models to perform single-cell RNA sequencing (scRNA-seq) analysis to investigate cell identity and driver genes related to dental mesenchymal cell differentiation during the late bell hard tissue formation stage. We identified seven main cell types and investigated the heterogeneity of mesenchymal cells. Subsequently, we identified novel cell marker genes, including
Pclo
in dental follicle cells,
Wnt10a
in pre-odontoblasts,
Fst
and
Igfbp2
in periodontal ligament cells, and validated the expression of
Igfbp3
in the apical pulp. The dynamic model revealed three differentiation trajectories within mesenchymal cells, originating from two types of dental follicle cells and apical pulp cells. Apical pulp cell differentiation is associated with the genes
Ptn
and
Satb2
, while dental follicle cell differentiation is associated with the genes
Tnc
,
Vim
,
Slc26a7
, and
Fgfr1
. Cluster-specific regulons were analyzed by pySCENIC. In addition, the odontogenic function of driver gene
TNC
was verified in the odontoblastic differentiation of human dental pulp stem cells. The expression of osteoclast differentiation factors was found to be increased in macrophages of the mandibular first molar.
Conclusions
Our results revealed the cell heterogeneity of molars in the late bell stage and identified driver genes associated with dental mesenchymal cell differentiation. These findings provide potential targets for diagnosing dental hard tissue diseases and tooth regeneration.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Animals
/ Bells
/ Biomedical and Life Sciences
/ Cell Differentiation - genetics
/ Cells
/ Dentin
/ Fibroblast growth factor receptor 1
/ Genes
/ Insulin-like growth factor-binding protein 2
/ Insulin-like growth factor-binding protein 3
/ Mandible
/ Mesenchymal Stem Cells - cytology
/ Mesenchymal Stem Cells - metabolism
/ Molar
/ Molars
/ Rats
/ RNA
/ Single-Cell Analysis - methods
/ Single-Cell Gene Expression Analysis
/ Single-cell RNA sequencing (scRNA-seq)
/ Teeth
/ TNC
