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  • Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.

Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.

Nature communications (2019-08-11)
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, Bing Hu
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.