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Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells

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dc.contributor.authorSrivastava, P.
dc.contributor.authorRomanazzo, S.
dc.contributor.authorKopecky, C.
dc.contributor.authorNemec, S.
dc.contributor.authorIreland, J.
dc.contributor.authorMolley, T.G.
dc.contributor.authorLin, K.
dc.contributor.authorJayathilaka, P.B.
dc.contributor.authorPandzic, E.
dc.contributor.authorYeola, A.
dc.contributor.authorChandrakanthan, V.
dc.contributor.authorPimanda, J.
dc.contributor.authorKilian, K.
dc.date.issued2022
dc.description.abstractGastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes-associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY-box transcription factor 17 (SOX17)+ T/BRACHYURY+ cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction-coupled wingless-type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts.
dc.description.statementofresponsibilityPallavi Srivastava, Sara Romanazzo, Chantal Kopecky, Stephanie Nemec, Jake Ireland, Thomas G. Molley, Kang Lin, Pavithra B. Jayathilaka, Elvis Pandzic, Avani Yeola, Vashe Chandrakanthan, John Pimanda, and Kristopher Kilian
dc.identifier.citationAdvanced Science, 2022; 10(5):2203614-1-2203614-16
dc.identifier.doi10.1002/advs.202203614
dc.identifier.issn2198-3844
dc.identifier.issn2198-3844
dc.identifier.orcidChandrakanthan, V. [0000-0002-4314-5029]
dc.identifier.urihttps://hdl.handle.net/2440/138058
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/arc/FT180100417
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1185021
dc.rights© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.source.urihttps://doi.org/10.1002/advs.202203614
dc.subjectembryogenesis; gastrulation; hydrogel; micropatterning; pluripotent stem cells
dc.subject.meshPluripotent Stem Cells
dc.subject.meshGerm Layers
dc.subject.meshHumans
dc.subject.meshMechanotransduction, Cellular
dc.subject.meshGastrulation
dc.subject.meshSOXF Transcription Factors
dc.subject.meshEpithelial-Mesenchymal Transition
dc.subject.meshCellular Microenvironment
dc.subject.meshYAP-Signaling Proteins
dc.titleDefined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells
dc.typeJournal article
pubs.publication-statusPublished

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