Open AccessCorneal Endothelial Cell Fate Is Maintained by LGR5 Through the Regulation of Hedgehog and Wnt Pathway
Author(s) -
HirataTominaga Kana,
Nakamura Takahiro,
Okumura Naoki,
Kawasaki Satoshi,
Kay Eunduck P.,
Barrandon Yann,
Koizumi Noriko,
Kinoshita Shigeru
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1390
Subject(s) - lgr5 , wnt signaling pathway , biology , microbiology and biotechnology , stem cell , progenitor cell , endothelial stem cell , signal transduction , genetics , in vitro
Abstract 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. S TEM C ells 2013;31:1396–1407