The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells.
WNT signaling is involved in maintaining stem cells in an undifferentiated state; however, it is often unclear which WNTs and WNT receptors are mediating these activities. Here we examined the role of the WNT receptor FZD7 in maintaining human embryonic stem cells (hESCs) in an undifferentiated and pluripotent state. FZD7 expression is significantly elevated in undifferentiated cells relative to differentiated cell populations, and interfering with its expression or function, either by short hairpin RNA-mediated knockdown or with a fragment antigen binding (Fab) molecule directed against FZD7, disrupts the pluripotent state of hESCs. The FZD7-specific Fab blocks signaling by Wnt3a protein by down-regulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/β-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/β-catenin signaling through FZD7 to maintain an undifferentiated phenotype.
Department of Cellular and Molecular Medicine, Stem Cell Program, University of California, San Diego, La Jolla, CA 92093-0695.
Antonio
A
Fernandez
Ian J
IJ
Huggins
Luca
L
Perna
David
D
Brafman
Desheng
D
Lu
Shiyin
S
Yao
Terry
T
Gaasterland
Dennis A
DA
Carson
Karl
K
Willert
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D051157:Frizzled Receptors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology*; D015398:Signal Transduction; D060509:Wnt3A Protein / Q000378:metabolism
C115810:FZD7 protein, human; D051157:Frizzled Receptors; D060509:Wnt3A Protein
differentiation; human pluripotent stem cell; self-renewal