Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation

Jemma Victoria Walker, Heng Zhuang, Donald Singer, Charlotte Sara Illsley, Wai Ling Kok, Kishor K. Sivaraj, Yan Gao, Chloe Bolton, Yuying Liu, Mengyuan Zhao, Portia Rebecca Clare Grayson, Shuang Wang, Jana Karbanová, Tim Lee, Stefano Ardu, Qingguo Lai, Jihui Liu, Moustapha Kassem, Shuo Chen, Kai Yang, Yuxing Bai, Christopher Tredwin, Alexander C. Zambon, Denis Corbeil, Ralf Adams, Basem M. Abdallah and Bing Hu ()
Additional contact information
Jemma Victoria Walker: University of Plymouth
Heng Zhuang: Peking University School and Hospital of Stomatology
Donald Singer: University of Plymouth
Charlotte Sara Illsley: University of Plymouth
Wai Ling Kok: University of Plymouth
Kishor K. Sivaraj: Department of Tissue Morphogenesis and University of Münster, Faculty of Medicine
Yan Gao: University of Plymouth
Chloe Bolton: University of Plymouth
Yuying Liu: University of Plymouth
Mengyuan Zhao: Capital Medical University
Portia Rebecca Clare Grayson: University of Plymouth
Shuang Wang: National University of Singapore
Jana Karbanová: Technische Universität Dresden
Tim Lee: Keck Graduate Institute
Stefano Ardu: Clinique Universitaire de Médecine Dentaire, Université de Genève
Qingguo Lai: the Second Hospital of Shandong University
Jihui Liu: Shenyang Stomatological Hospital
Moustapha Kassem: Odense University Hospital & University of Southern Denmark
Shuo Chen: The University of Texas Health Science Center at San Antonio
Kai Yang: Capital Medical University
Yuxing Bai: Capital Medical University
Christopher Tredwin: University of Plymouth
Alexander C. Zambon: Keck Graduate Institute
Denis Corbeil: Technische Universität Dresden
Ralf Adams: Department of Tissue Morphogenesis and University of Münster, Faculty of Medicine
Basem M. Abdallah: Odense University Hospital & University of Southern Denmark
Bing Hu: University of Plymouth

Nature Communications, 2019, vol. 10, issue 1, 1-18

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11611-0

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