The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

Antonio Fernandez; Ian J. Huggins; Luca Perna; David Brafman; Desheng Lu; Shiyin Yao; Terry Gaasterland; Dennis A. Carson; Karl Willert

doi:10.1073/pnas.1323697111

The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

Antonio Fernandez, Ian J. Huggins, Luca Perna, David Brafman, Desheng Lu, Shiyin Yao, Terry Gaasterland, Dennis A. Carson, Karl Willert

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72 Scopus citations

Abstract

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 downregulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/?-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/?-catenin signaling through FZD7 to maintain an undifferentiated phenotype.

Original language	English (US)
Pages (from-to)	1409-1414
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	111
Issue number	4
DOIs	https://doi.org/10.1073/pnas.1323697111
State	Published - Jan 28 2014
Externally published	Yes

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Fernandez, A., Huggins, I. J., Perna, L., Brafman, D., Lu, D., Yao, S., Gaasterland, T., Carson, D. A., & Willert, K. (2014). The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells. Proceedings of the National Academy of Sciences of the United States of America, 111(4), 1409-1414. https://doi.org/10.1073/pnas.1323697111

Fernandez, A, Huggins, IJ, Perna, L, Brafman, D, Lu, D, Yao, S, Gaasterland, T, Carson, DA & Willert, K 2014, 'The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 4, pp. 1409-1414. https://doi.org/10.1073/pnas.1323697111

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abstract = "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 downregulating FZD7 protein levels, suggesting that FZD7 transduces Wnt signals to activate Wnt/?-catenin signaling. These results demonstrate that FZD7 encodes a regulator of the pluripotent state and that hESCs require endogenous WNT/?-catenin signaling through FZD7 to maintain an undifferentiated phenotype.",

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The WNT receptor FZD7 is required for maintenance of the pluripotent state in human embryonic stem cells

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