| 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. |
| 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. |
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