Selective activation of FZD7 promotes mesendodermal differentiation of human pluripotent stem cells
- University of California, San Diego, United States
- San Diego State University, United States
Abstract
WNT proteins are secreted symmetry breaking signals that interact with cell surface receptors of the FZD family to regulate a multitude of developmental processes. Studying selectivity between WNTs and FZDs has been hampered by the paucity of purified WNT proteins and by their apparent non-selective interactions with the FZD receptors. Here we describe an engineered protein, called F7L6, comprised of antibody-derived single chain variable fragments, that selectively binds to human FZD7 and the co-receptor LRP6. F7L6 potently activates WNT/b-catenin signaling in a manner similar to Wnt3a. In contrast to Wnt3a, F7L6 engages only FZD7 and none of the other FZD proteins. Treatment of human pluripotent stem (hPS) cells with F7L6 initiates transcriptional programs similar to those observed during primitive streak formation and subsequent gastrulation in the mammalian embryo. This demonstrates that selective engagement and activation of FZD7 signaling is sufficient to promote mesendodermal differentiation of hPS cells.
Data availability
The RNA-seq and ChIP-seq data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE158121.
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Selective activation of FZD7 in human pluripotent stem cellsNCBI Gene Expression Omnibus, GSE158121.
Article and author information
Author details
Funding
National Institutes of Health (R35GM134961)
- Karl Willert
National Institutes of Health (S10OD026929)
- Karl Willert
National Cancer Institute (T32 CA067754,graduate student fellowship to Myan Do)
- Myan Do
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Yi Arial Zeng, Chinese Academy of Sciences, China
Version history
- Received: September 13, 2020
- Accepted: December 16, 2020
- Accepted Manuscript published: December 17, 2020 (version 1)
- Version of Record published: December 24, 2020 (version 2)
Copyright
© 2020, Gumber et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Selective activation of FZD7 promotes mesendodermal differentiation of human pluripotent stem cells
eLife 9:e63060.
https://doi.org/10.7554/eLife.63060
Further reading
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