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Tissue-Specific Stem Cells
Article first published online: 5 JUL 2013
Copyright © 2013 AlphaMed Press
Volume 31, Issue 7, pages 1396–1407, July 2013
How to Cite
Hirata-Tominaga, K., Nakamura, T., Okumura, N., Kawasaki, S., Kay, E. P., Barrandon, Y., Koizumi, N. and Kinoshita, S. (2013), Corneal Endothelial Cell Fate Is Maintained by LGR5 Through the Regulation of Hedgehog and Wnt Pathway. STEM CELLS, 31: 1396–1407. doi: 10.1002/stem.1390
Author contributions: K.H.-T.: provision of study material or patients, collection and/or assembly of data; T.N.: conception and design, collection and/or assembly of data, data analysis and interpretation, writing manuscript; N.O.: collection and/or assembly of data, S. KAWASAKI: collection and/or assembly of data; E.P.K.: data analysis and interpretation; Y.B.: financial support; N.K.: data analysis and interpretation; financial support; S. KINOSHITA: collection and/or assembly of data. K.H.T. and T.N. contributed equally to this article.
Disclosure of potential conflicts of interest is found at the end of this article.
first published online in STEM CELLS EXPRESS April 3, 2013.
- Issue published online: 5 JUL 2013
- Article first published online: 5 JUL 2013
- Accepted manuscript online: 3 APR 2013 05:24AM EST
- Manuscript Accepted: 4 MAR 2013
- Manuscript Received: 18 SEP 2012
- Grants-in-Aid for scientific research
- Highway Program for realization of regenerative medicine
- JST-ETH Strategic Japanese-Swiss Cooperative Program and OptiStem
- Stem cell;
Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), a target of Wnt signaling, is reportedly a marker of intestine, stomach, and hair follicle stem cells in mice. To gain a novel insight into the role of LGR5 in human corneal tissue, we performed gain- and loss-of-function studies. The findings of this study show for the first time that LGR5 is uniquely expressed in the peripheral region of human corneal endothelial cells (CECs) and that LGR5(+) cells have some stem/progenitor cell characteristics, and that in human corneal endothelium, LGR5 is the target molecule and negative feedback regulator of the Hedgehog (HH) signaling pathway. Interestingly, the findings of this study show that persistent LGR5 expression maintained endothelial cell phenotypes and inhibited mesenchymal transformation (MT) through the Wnt pathway. Moreover, R-spondin-1, an LGR5 ligand, dramatically accelerated CEC proliferation and also inhibited MT through the Wnt pathway. These findings provide new insights into the underlying homeostatic regulation of human corneal endothelial stem/progenitor cells by LGR5 through the HH and Wnt pathways. STEM Cells2013;31:1396–1407