Title High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation-associated versus preneurulation-associated fate patterning
Authors Tewary, Mukul, Dziedzicka, Dominika, Ostblom, Joel, Prochazka, Laura, Shakiba, Nika, Heydari, Tiam, Aguilar-Hidalgo, Daniel, Woodford, Curtis, Piccinini, Elia, BECERRA ALONSO, DAVID, Vickers, Alice, Louis, Blaise, Rahman, Nafees, Danovi, Davide, Geens, Mieke, Watt, Fiona M., Zandstra, Peter W., BECERRA ALONSO, DAVID
External publication No
Means PLoS. Biol.
Scope Article
Nature Científica
JCR Quartile 1
SJR Quartile 1
JCR Impact 7.07600
Area International
Web https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074378026&doi=10.1371%2fjournal.pbio.3000081&partnerID=40&md5=4e2dfd8bd478690bdfcad00290fa40f7
Publication date 01/10/2019
ISI 000505712400001
Scopus Id 2-s2.0-85074378026
DOI 10.1371/journal.pbio.3000081
Abstract In vitro models of postimplantation human development are valuable to the fields of regenerative medicine and developmental biology. Here, we report characterization of a robust in vitro platform that enabled high-content screening of multiple human pluripotent stem cell (hPSC) lines for their ability to undergo peri-gastrulation-like fate patterning upon bone morphogenetic protein 4 (BMP4) treatment of geometrically confined colonies and observed significant heterogeneity in their differentiation propensities along a gastrulation associable and neuralization associable axis. This cell line-associated heterogeneity was found to be attributable to endogenous Nodal expression, with up-regulation of Nodal correlated with expression of a gastrulation-associated gene profile, and Nodal down-regulation correlated with a preneurulation-associated gene profile expression. We harness this knowledge to establish a platform of preneurulation-like fate patterning in geometrically confined hPSC colonies in which fates arise because of a BMPs signalling gradient conveying positional information. Our work identifies a Nodal signalling-dependent switch in peri-gastrulation versus preneurulation-associated fate patterning in hPSC cells, provides a technology to robustly assay hPSC differentiation outcomes, and suggests conserved mechanisms of organized fate specification in differentiating epiblast and ectodermal tissues.
Keywords bone morphogenetic protein 4; morphogen; protein Nodal; Article; cell differentiation; controlled study; correlational study; down regulation; embryo; embryo pattern formation; gastrulation; genetic a
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