CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche

Tamaki Yokohama-Tamaki, Keishi Otsu, Hidemitsu Harada, Shunichi Shibata, Nobuko Obara, Kazuharu Irie, Akiyoshi Taniguchi, Takashi Nagasawa, Kazunari Aoki, Steven R. Caliari, Daniel W. Weisgerber, Brendan A C Harley

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Dental stem cells are located at the proximal ends of rodent incisors. These stem cells reside in the dental epithelial stem cell niche, termed the apical bud. We focused on identifying critical features of a chemotactic signal in the niche. Here, we report that CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in dental stem cell niche cells. We report cells in the apical bud express CXCR4 mRNA at high levels while expression is restricted in the basal epithelium (BE) and transit-amplifying (TA) cell regions. Furthermore, the CXCL12 ligand is present in mesenchymal cells adjacent to the apical bud. We then performed gain- and loss-of-function analyses to better elucidate the role of CXCR4 and CXCL12. CXCR4-deficient mice contain epithelial cell aggregates, while cell proliferation in mutant incisors was also significantly reduced. We demonstrate in vitro that dental epithelial cells migrate toward sources of CXCL12, whereas knocking down CXCR4 impaired motility and resulted in formation of dense cell colonies. These results suggest that CXCR4 expression may be critical for activation of enamel progenitor cell division and that CXCR4/CXCL12 signaling may control movement of epithelial progenitors from the dental stem cell niche.

Original languageEnglish
Pages (from-to)633-642
Number of pages10
JournalCell and Tissue Research
Volume362
Issue number3
DOIs
Publication statusPublished - 2015 Dec 1
Externally publishedYes

Fingerprint

Stem Cell Niche
Dental Enamel
Cell Movement
Tooth
Stem Cells
Cell Proliferation
Epithelial Cells
Incisor
Cell Division
Rodentia
Epithelium
Ligands
Messenger RNA

Keywords

  • CXCR4/CXCL12 signal
  • Dental stem cell niche
  • Migration
  • Proliferation
  • Tooth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

Cite this

Yokohama-Tamaki, T., Otsu, K., Harada, H., Shibata, S., Obara, N., Irie, K., ... Harley, B. A. C. (2015). CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche. Cell and Tissue Research, 362(3), 633-642. https://doi.org/10.1007/s00441-015-2248-y

CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche. / Yokohama-Tamaki, Tamaki; Otsu, Keishi; Harada, Hidemitsu; Shibata, Shunichi; Obara, Nobuko; Irie, Kazuharu; Taniguchi, Akiyoshi; Nagasawa, Takashi; Aoki, Kazunari; Caliari, Steven R.; Weisgerber, Daniel W.; Harley, Brendan A C.

In: Cell and Tissue Research, Vol. 362, No. 3, 01.12.2015, p. 633-642.

Research output: Contribution to journalArticle

Yokohama-Tamaki, T, Otsu, K, Harada, H, Shibata, S, Obara, N, Irie, K, Taniguchi, A, Nagasawa, T, Aoki, K, Caliari, SR, Weisgerber, DW & Harley, BAC 2015, 'CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche', Cell and Tissue Research, vol. 362, no. 3, pp. 633-642. https://doi.org/10.1007/s00441-015-2248-y
Yokohama-Tamaki, Tamaki ; Otsu, Keishi ; Harada, Hidemitsu ; Shibata, Shunichi ; Obara, Nobuko ; Irie, Kazuharu ; Taniguchi, Akiyoshi ; Nagasawa, Takashi ; Aoki, Kazunari ; Caliari, Steven R. ; Weisgerber, Daniel W. ; Harley, Brendan A C. / CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche. In: Cell and Tissue Research. 2015 ; Vol. 362, No. 3. pp. 633-642.
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