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Article

Multifactorial Modeling Reveals a Dominant Role of Wnt Signaling in Lineage Commitment of Human Pluripotent Stem Cells

1
iBB—Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
2
The Discoveries Centre for Regenerative and Precision Medicine, Lisbon Campus, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisbon, Portugal
*
Author to whom correspondence should be addressed.
Bioengineering 2019, 6(3), 71; https://doi.org/10.3390/bioengineering6030071
Received: 5 July 2019 / Revised: 8 August 2019 / Accepted: 13 August 2019 / Published: 15 August 2019
(This article belongs to the Special Issue Stem Cell and Biologic Scaffold Engineering)
The human primed pluripotent state is maintained by a complex balance of several signaling pathways governing pluripotency maintenance and commitment. Here, we explore a multiparameter approach using a full factorial design and a simple well-defined culture system to assess individual and synergistic contributions of Wnt, FGF and TGFβ signaling to pluripotency and lineage specification of human induced pluripotent stem cells (hiPSC). Hierarchical clustering and quadratic models highlighted a dominant effect of Wnt signaling over FGF and TGFβ signaling, drawing hiPSCs towards mesendoderm lineages. In addition, a synergistic effect between Wnt signaling and FGF was observed to have a negative contribution to pluripotency maintenance and a positive contribution to ectoderm and mesoderm commitment. Furthermore, FGF and TGFβ signaling only contributed significantly for negative ectoderm scores, suggesting that the effect of both factors for pluripotency maintenance resides in a balance of inhibitory signals instead of proactive stimulation of hiPSC pluripotency. Overall, our dry-signaling multiparameter modeling approach can contribute to elucidate individual and synergistic inputs, providing an additional degree of comprehension of the complex regulatory mechanisms of human pluripotency and commitment. View Full-Text
Keywords: multiparameter; factorial design; Wnt signaling; TGFβ signaling; FGF signaling; human induced pluripotent stem cells; pluripotency and commitment multiparameter; factorial design; Wnt signaling; TGFβ signaling; FGF signaling; human induced pluripotent stem cells; pluripotency and commitment
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MDPI and ACS Style

Dias, T.P.; Fernandes, T.G.; Diogo, M.M.; Cabral, J.M.S. Multifactorial Modeling Reveals a Dominant Role of Wnt Signaling in Lineage Commitment of Human Pluripotent Stem Cells. Bioengineering 2019, 6, 71. https://doi.org/10.3390/bioengineering6030071

AMA Style

Dias TP, Fernandes TG, Diogo MM, Cabral JMS. Multifactorial Modeling Reveals a Dominant Role of Wnt Signaling in Lineage Commitment of Human Pluripotent Stem Cells. Bioengineering. 2019; 6(3):71. https://doi.org/10.3390/bioengineering6030071

Chicago/Turabian Style

Dias, Tiago P., Tiago G. Fernandes, Maria M. Diogo, and Joaquim M.S. Cabral. 2019. "Multifactorial Modeling Reveals a Dominant Role of Wnt Signaling in Lineage Commitment of Human Pluripotent Stem Cells" Bioengineering 6, no. 3: 71. https://doi.org/10.3390/bioengineering6030071

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