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- W2980821730 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." @default.
- W2980821730 created "2019-10-25" @default.
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- W2980821730 date "2019-10-21" @default.
- W2980821730 modified "2023-10-17" @default.
- W2980821730 title "High-throughput micropatterning platform reveals Nodal-dependent bisection of peri-gastrulation–associated versus preneurulation-associated fate patterning" @default.
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- W2980821730 doi "https://doi.org/10.1371/journal.pbio.3000081" @default.
- W2980821730 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6822778" @default.
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- W2980821730 hasPublicationYear "2019" @default.
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