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Nat Commun. 2019 Aug 9;10(1):3596. doi: 10.1038/s41467-019-11611-0.

Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.

Author information

1
Stem Cells & Regenerative Medicine Laboratory, Peninsula Dental School, University of Plymouth, 16 Research Way, Plymouth, PL6 8BU, UK.
2
Department of Cariology, Endodontology and Operative Dentistry, Peking University School and Hospital of Stomatology, 22 South Zhongguancun Avenue, Haidian District, 100081, Beijing, China.
3
Taikang Bybo Dental Group Beijing, No. 4 Building, 18 Qinian Avenue, Dong Cheng District, 100062, Beijing, China.
4
Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and University of Münster, Faculty of Medicine, 48149, Münster, Germany.
5
Department of Orthodontics, School of Stomatology, Capital Medical University, 4 Tian Tan Xi Li, Dong Cheng District, 100050, Beijing, China.
6
Department of Orthodontics, Shenyang Stomatological Hospital, 38 Zhong Shan Road, He Ping District, 110002, Shen Yang, China.
7
Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, 4 Tian Tan Xi Li, Dong Cheng District, 10050, Beijing, China.
8
Faculty of Dentistry, National University of Singapore, 11 Lower Kent Ridge Road, Singapore, 119083, Singapore.
9
Tissue Engineering Laboratories (BIOTEC), Technische Universität Dresden, 01307, Dresden, Germany.
10
Department of Biopharmaceutical Sciences, Keck Graduate Institute, 535 Watson Drive, Claremont, CA, 91711, USA.
11
Clinique Universitaire de Médecine Dentaire, Université de Genève, 19 rue Lombard, Geneva, CH-1206, Switzerland.
12
Department of Oral and Maxillofacial Surgery, the Second Hospital of Shandong University, 247 Beiyuan Street, 250033, Jinan, China.
13
Research Center of 3D Printing in Stomatology of Shandong University, 247 Beiyuan Street, 250033, Jinan, China.
14
Molecular Endocrinology Lab (KMEB), Department of Endocrinology, Odense University Hospital & University of Southern Denmark, 5000, Odense, Denmark.
15
Department of Cellular and Molecular Medicine, DanStem (Danish Stem Cell Center), Panum Institute, University of Copenhagen, 2200, Copenhagen, Denmark.
16
Department of Developmental Dentistry, Dental School, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.
17
Department of Biological Sciences, College of Science, King Faisal University, Hofuf, 11533, Saudi Arabia.
18
Stem Cells & Regenerative Medicine Laboratory, Peninsula Dental School, University of Plymouth, 16 Research Way, Plymouth, PL6 8BU, UK. bing.hu@plymouth.ac.uk.

Abstract

Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1's function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.

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