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Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation

Joseph Masseya, Yida Liua, Omar Alvarengaa, Teresa Saeza, Matthew Schmerera, Aryeh Warmflasha
doi: https://doi.org/10.1101/406306
Joseph Masseya
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
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Yida Liua
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
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Omar Alvarengaa
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
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Teresa Saeza
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
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Matthew Schmerera
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
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Aryeh Warmflasha
aDepartment of Biosciences, Rice University, Houston, Texas, 77005
bDepartment of Bioengineering, Rice University, Houston, Texas, 77005
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  • For correspondence: aryeh.warmflash@rice.edu
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Abstract

WNT/ß-catenin signaling is crucial to all stages of life. It controls early morphogenetic events in embryos, maintains stem-cell niches in adults, and is disregulated in many types of cancer. Despite its ubiquity, little is known about the dynamics of signal transduction or whether it varies across contexts. Here we probe the dynamics of signaling by monitoring nuclear accumulation of ß-catenin, the primary transducer of canonical WNT signals, using quantitative live-cell imaging. We show that ß-catenin signaling responds adaptively to constant WNT signaling in pluripotent stem cells, and that these dynamics become sustained upon differentiation. Varying dynamics were also observed in the response to WNT in commonly used mammalian cell-lines. Signal attenuation in pluripotent cells is controlled by both intra- and extra-cellular negative regulation of WNT signaling. TGFß-superfamily ligands Activin and BMP, which coordinate with WNT signaling to pattern the gastrula, increase the ß-catenin response in a manner independent of their ability to induce new WNT-ligand production. Our results reveal how variables external to the pathway, including differentiation status and crosstalk with other pathways, dramatically alter WNT/ß-catenin dynamics.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted September 22, 2018.
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Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation
Joseph Masseya, Yida Liua, Omar Alvarengaa, Teresa Saeza, Matthew Schmerera, Aryeh Warmflasha
bioRxiv 406306; doi: https://doi.org/10.1101/406306
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Synergy with TGFß ligands switches WNT pathway dynamics from transient to sustained during human pluripotent cell differentiation
Joseph Masseya, Yida Liua, Omar Alvarengaa, Teresa Saeza, Matthew Schmerera, Aryeh Warmflasha
bioRxiv 406306; doi: https://doi.org/10.1101/406306

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