Título High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation-associated versus preneurulation-associated fate patterning
Autores 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.
Publicación externa No
Alcance Article
Naturaleza Científica
Cuartil JCR 1
Cuartil SJR 1
Impacto JCR 7.076
Impacto SJR 4.488
Web https://www.scopus.com/inward/record.uri?eid=2-s2.0-85074378026&doi=10.1371%2fjournal.pbio.3000081&partnerID=40&md5=4e2dfd8bd478690bdfcad00290fa40f7
Fecha de publicacion 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\n the fields of regenerative medicine and developmental biology. Here, we\n report characterization of a robust in vitro platform that enabled\n high-content screening of multiple human pluripotent stem cell (hPSC)\n lines for their ability to undergo peri-gastrulation-like fate\n patterning upon bone morphogenetic protein 4 (BMP4) treatment of\n geometrically confined colonies and observed significant heterogeneity\n in their differentiation propensities along a gastrulation associable\n and neuralization associable axis. This cell line-associated\n heterogeneity was found to be attributable to endogenous Nodal\n expression, with up-regulation of Nodal correlated with expression of a\n gastrulation-associated gene profile, and Nodal down-regulation\n correlated with a preneurulation-associated gene profile expression. We\n harness this knowledge to establish a platform of preneurulation-like\n fate patterning in geometrically confined hPSC colonies in which fates\n arise because of a BMPs signalling gradient conveying positional\n information. Our work identifies a Nodal signalling-dependent switch in\n peri-gastrulation versus preneurulation-associated fate patterning in\n hPSC cells, provides a technology to robustly assay hPSC differentiation\n outcomes, and suggests conserved mechanisms of organized fate\n specification in differentiating epiblast and ectodermal tissues.
Palabras clave bone morphogenetic protein 4; morphogen; protein Nodal; Article; cell differentiation; controlled study; correlational study; down regulation; embryo; embryo pattern formation; gastrulation; genetic association; genetic fingerprinting; geometry; human; human cell; neurulation; pluripotent stem cell line; protein expression; upregulation
Miembros de la Universidad Loyola

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