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...
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doaj-64a204ac32c34ba3a70a8988bd0c27802020-11-25T00:29:25ZengPeerJ Inc.PeerJ2167-83592016-02-014e168410.7717/peerj.1684Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysisYunfei Zheng0Lingfei Jia1Pengfei Liu2Dandan Yang3Waner Hu4Shubin Chen5Yuming Zhao6Jinglei Cai7Duanqing Pei8Lihong Ge9Shicheng Wei10Department of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, ChinaDepartment of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, ChinaInstitute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaInstitute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, ChinaInstitute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, ChinaInstitute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaInstitute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, ChinaDepartment of Oral and Maxillofacial Surgery, Laboratory of Interdisciplinary Studies, Peking University School and Hospital of Stomatology, Beijing, ChinaBackground. 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.https://peerj.com/articles/1684.pdfOdontogenesisOdontogenic potentialRNA-SeqTranscriptomeMouse dental mesenchymal cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yunfei Zheng Lingfei Jia Pengfei Liu Dandan Yang Waner Hu Shubin Chen Yuming Zhao Jinglei Cai Duanqing Pei Lihong Ge Shicheng Wei |
spellingShingle |
Yunfei Zheng Lingfei Jia Pengfei Liu Dandan Yang Waner Hu Shubin Chen Yuming Zhao Jinglei Cai Duanqing Pei Lihong Ge Shicheng Wei Insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis PeerJ Odontogenesis Odontogenic potential RNA-Seq Transcriptome Mouse dental mesenchymal cells |
author_facet |
Yunfei Zheng Lingfei Jia Pengfei Liu Dandan Yang Waner Hu Shubin Chen Yuming Zhao Jinglei Cai Duanqing Pei Lihong Ge Shicheng Wei |
author_sort |
Yunfei Zheng |
title |
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_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_sort |
insight into the maintenance of odontogenic potential in mouse dental mesenchymal cells based on transcriptomic analysis |
publisher |
PeerJ Inc. |
series |
PeerJ |
issn |
2167-8359 |
publishDate |
2016-02-01 |
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. |
topic |
Odontogenesis Odontogenic potential RNA-Seq Transcriptome Mouse dental mesenchymal cells |
url |
https://peerj.com/articles/1684.pdf |
work_keys_str_mv |
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