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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 3596 |
| Tidsskrift | Nature Communications |
| Vol/bind | 10 |
| Udgave nummer | 1 |
| Antal sider | 18 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 9. aug. 2019 |
Finansiering
We would like to thank G.P. Dotto for initial support of the project; M.C. Reymond for assisting SEM; N. Ditzel for technical assistance of animal breeding, and A. Miyawaki for mAG-hGeminin (1/110)-pCSII-EF-MCS and mCherry-hCdt1(30/120)-pCSII-EF-MCS vectors. This work was supported by the National Natural Science Foundation of China to H.Z. (30801289 and 81371138), National Institutes of Health to S.C. (RO1DE019802), the Deutsche Forschungsgemeinschaft (SFB 655 B3) to D.C., the European Union Marie Skłodowska-Curie Actions (618930, OralStem FP7-PEOPLE-2013-CIG), the European Regional Development Fund and the Biotechnology and Biological Sciences Research Council of the UK (BB/L02392X/1) to B.H.
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