TY - JOUR
T1 - CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche
AU - Yokohama-Tamaki, Tamaki
AU - Otsu, Keishi
AU - Harada, Hidemitsu
AU - Shibata, Shunichi
AU - Obara, Nobuko
AU - Irie, Kazuharu
AU - Taniguchi, Akiyoshi
AU - Nagasawa, Takashi
AU - Aoki, Kazunari
AU - Caliari, Steven R.
AU - Weisgerber, Daniel W.
AU - Harley, Brendan A.C.
N1 - Funding Information:
We are grateful to Dr. Stephanie Tsang (University of Illinois at Urbana-Champaign), Dr. Myung-Eun Shin (Duke University Medical Center), and Ms. Yanzhen Li, M.A. (University of North Carolina) for critical discussions; to Mr. Naoyuki Tamaki (IBM Global Services Japan Solution and Services Company ISOL) for technical support in generating beautiful figures; Dr. Yuko Suzuki (Health Sciences University of Hokkaido) for excellent suggestions and for providing materials. This work was supported by JSPS KAKENHI Grant Numbers 19791342, 15K20358 to Y-T. T. We are also grateful for the funding for this study provided by the Chemistry-Biology Interface Training Program NIH NIGMS T32GM070421 (SRC) as well as the Chemical and Biomolecular Engineering Dept. (BAH), and the Institute for Genomic Biology (BAH) at the University of Illinois at Urbana-Champaign.
Publisher Copyright:
© 2015, Springer-Verlag Berlin Heidelberg.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - CXCR4/CXCL12 signal
KW - Dental stem cell niche
KW - Migration
KW - Proliferation
KW - Tooth
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U2 - 10.1007/s00441-015-2248-y
DO - 10.1007/s00441-015-2248-y
M3 - Article
C2 - 26246398
AN - SCOPUS:84949529642
SN - 0302-766X
VL - 362
SP - 633
EP - 642
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 3
ER -