Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jun 26, 2023; 15(6): 589-606
Published online Jun 26, 2023. doi: 10.4252/wjsc.v15.i6.589
Single cell RNA sequencing reveals mesenchymal heterogeneity and critical functions of Cd271 in tooth development
Yan-Yan Zhang, Feng Li, Xiao-Ke Zeng, Yan-Hui Zou, Bing-Bing Zhu, Jia-Jia Ye, Yun-Xiao Zhang, Qiu Jin, Xin Nie
Yan-Yan Zhang, Feng Li, Xiao-Ke Zeng, Yan-Hui Zou, Bing-Bing Zhu, Jia-Jia Ye, Yun-Xiao Zhang, Qiu Jin, Xin Nie, School & Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, Zhejiang Province, China
Author contributions: Zhang YY conceived experiments, interpreted data and wrote a manuscript; Li F, Zeng XK and Zou YH performed the experiment; Zhu BB, Ye JJ, Zhang YX, and Jin Q provided a critical insight into this study; Nie X supervised this study; All authors read and approved the final version for submission.
Supported by National Natural Science Foundation of China (General Program), No. 31870971; and Medical Health Science and Technology Project of Zhejiang Province, No. 2023KY155.
Institutional animal care and use committee statement: All animal experiments were performed according to the protocols approved by the Medical Ethics Committee of Wenzhou Medical University, No. wydw2019-0224.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets analyzed for this study can be found in the NCBI SRA: 506PRJNA891206. https://www.ncbi.nlm.nih.gov/sra/PRJNA891206.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xin Nie, PhD, Professor, School & Hospital of Stomatology, Wenzhou Medical University, Xueyuan West Road, Lucheng District, Wenzhou 325027, Zhejiang Province, China. dr.xinnie@qq.com
Received: February 9, 2023
Peer-review started: February 9, 2023
First decision: April 10, 2023
Revised: April 18, 2023
Accepted: May 5, 2023
Article in press: May 5, 2023
Published online: June 26, 2023
Processing time: 137 Days and 8.9 Hours
ARTICLE HIGHLIGHTS
Research background

Tooth loss has become a common problem in human life. Compared with traditional denture restoration, dental tissue engineering has become the most ideal means to solve this problem, and it is also one of the most active research fields of stomatology in recent years. The tooth development involves complex signal pathways. Ecto-mesenchymal stem cells (MSCs) were regarded as the primitive dental cells in the classical theory of tooth development. To date, in-depth studies of the odontogenesis and osteogenesis of MSCs are still lacking.

Research motivation

We contribute to thorough exploration of the mechanism of odontogenesis and osteogenesis to add to the theory of tooth development.

Research objectives

Our study provides novel insights into the biological features of MSCs at the single cell level and the mechanism of Cd271 in regulating odontogenesis and osteogenesis.

Research methods

We used the maxillary process from mouse embryos as a model to understand the development of maxillary-process-derived MSCs. We applied single cell RNA sequence analysis to elucidate the cellular heterogeneity and explore molecular details. And we verified the findings from single cell sequencing in vitro by lab experience such as cell staining, cell counting and quantitative real time polymerase chain reaction.

Research results

Our study reveals: (1) High cellular heterogeneity and molecular details; (2) Significant functional and signaling differences between cell types; (3) Novel subclusters of mesenchymal stem cells; and (4) Crucial cell-cell interactions of mesenchymal subpopulations. Besides, we contribute to thorough exploration of the mechanism of Cd271 in regulating odontogenesis and osteogenesis.

Research conclusions

Our study reveals high cellular heterogeneity, molecular details and cell-cell interactions in MSCs. We found significant functional and signaling differences between Cd271 knockout and wildtype MSCs. We clarified that Cd271 is significantly associated with the regulation of mineralization.

Research perspectives

We need illustrate that Mdk signaling is involved in the regulatory mechanism of mineralization in future research. And direct mechanisms of Cd271 involved in tooth development are needed in further studies.