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Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis
Background. Mouse dental mesenchymal cells (mDMCs) from tooth germs of cap or later stages are frequently used in the context of developmental biology or whole-tooth regeneration due to their odontogenic potential. In vitro-expanded mDMCs serve as an alternative cell source considering the difficult...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
PeerJ Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768683/ https://www.ncbi.nlm.nih.gov/pubmed/26925321 http://dx.doi.org/10.7717/peerj.1684 |
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author | Zheng, Yunfei Jia, Lingfei Liu, Pengfei Yang, Dandan Hu, Waner Chen, Shubin Zhao, Yuming Cai, Jinglei Pei, Duanqing Ge, Lihong Wei, Shicheng |
author_facet | Zheng, Yunfei Jia, Lingfei Liu, Pengfei Yang, Dandan Hu, Waner Chen, Shubin Zhao, Yuming Cai, Jinglei Pei, Duanqing Ge, Lihong Wei, Shicheng |
author_sort | Zheng, Yunfei |
collection | PubMed |
description | Background. Mouse dental mesenchymal cells (mDMCs) from tooth germs of cap or later stages are frequently used in the context of developmental biology or whole-tooth regeneration due to their odontogenic potential. In vitro-expanded mDMCs serve as an alternative cell source considering the difficulty in obtaining primary mDMCs; however, cultured mDMCs fail to support tooth development as a result of functional failures of specific genes or pathways. The goal of this study was to identify the genes that maintain the odontogenic potential of mDMCs in culture. Methods. We examined the odontogenic potential of freshly isolated versus cultured mDMCs from the lower first molars of embryonic day 14.5 mice. The transcriptome of mDMCs was detected using RNA sequencing and the data were validated by qRT-PCR. Differential expression analysis and pathway analysis were conducted to identify the genes that contribute to the loss of odontogenic potential. Results. Cultured mDMCs failed to develop into well-structured tooth when they were recombined with dental epithelium. Compared with freshly isolated mDMCs, we found that 1,004 genes were upregulated and 948 were downregulated in cultured mDMCs. The differentially expressed genes were clustered in the biological processes and signaling pathways associated with tooth development. Following in vitro culture, genes encoding a wide array of components of MAPK, TGF-β/BMP, and Wnt pathways were significantly downregulated. Moreover, the activities of Bdnf, Vegfα, Bmp2, and Bmp7 were significantly inhibited in cultured mDMCs. Supplementation of VEGFα, BMP2, and BMP7 restored the expression of a subset of downregulated genes and induced mDMCs to form dentin-like structures in vivo. Conclusions. Vegfα, Bmp2, and Bmp7 play a role in the maintenance of odontogenic potential in mDMCs. |
format | Online Article Text |
id | pubmed-4768683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | PeerJ Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-47686832016-02-26 Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis Zheng, Yunfei Jia, Lingfei Liu, Pengfei Yang, Dandan Hu, Waner Chen, Shubin Zhao, Yuming Cai, Jinglei Pei, Duanqing Ge, Lihong Wei, Shicheng PeerJ Bioinformatics Background. Mouse dental mesenchymal cells (mDMCs) from tooth germs of cap or later stages are frequently used in the context of developmental biology or whole-tooth regeneration due to their odontogenic potential. In vitro-expanded mDMCs serve as an alternative cell source considering the difficulty in obtaining primary mDMCs; however, cultured mDMCs fail to support tooth development as a result of functional failures of specific genes or pathways. The goal of this study was to identify the genes that maintain the odontogenic potential of mDMCs in culture. Methods. We examined the odontogenic potential of freshly isolated versus cultured mDMCs from the lower first molars of embryonic day 14.5 mice. The transcriptome of mDMCs was detected using RNA sequencing and the data were validated by qRT-PCR. Differential expression analysis and pathway analysis were conducted to identify the genes that contribute to the loss of odontogenic potential. Results. Cultured mDMCs failed to develop into well-structured tooth when they were recombined with dental epithelium. Compared with freshly isolated mDMCs, we found that 1,004 genes were upregulated and 948 were downregulated in cultured mDMCs. The differentially expressed genes were clustered in the biological processes and signaling pathways associated with tooth development. Following in vitro culture, genes encoding a wide array of components of MAPK, TGF-β/BMP, and Wnt pathways were significantly downregulated. Moreover, the activities of Bdnf, Vegfα, Bmp2, and Bmp7 were significantly inhibited in cultured mDMCs. Supplementation of VEGFα, BMP2, and BMP7 restored the expression of a subset of downregulated genes and induced mDMCs to form dentin-like structures in vivo. Conclusions. Vegfα, Bmp2, and Bmp7 play a role in the maintenance of odontogenic potential in mDMCs. PeerJ Inc. 2016-02-22 /pmc/articles/PMC4768683/ /pubmed/26925321 http://dx.doi.org/10.7717/peerj.1684 Text en ©2016 Zheng et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited. |
spellingShingle | Bioinformatics Zheng, Yunfei Jia, Lingfei Liu, Pengfei Yang, Dandan Hu, Waner Chen, Shubin Zhao, Yuming Cai, Jinglei Pei, Duanqing Ge, Lihong Wei, Shicheng Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title | Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title_full | Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title_fullStr | Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title_full_unstemmed | Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title_short | Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
title_sort | insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768683/ https://www.ncbi.nlm.nih.gov/pubmed/26925321 http://dx.doi.org/10.7717/peerj.1684 |
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