High-throughput Micropatterning Platform Reveals Nodal-dependent Bisection of Peri-gastrulation-associated Versus Preneurulation-associated Fate Patterning

Overview

Journal PLoS Biol

Specialty Biology

Date 2019 Oct 22

PMID 31634368

Citations 18

Authors

Mukul Tewary

Dominika Dziedzicka

Joel Ostblom

Laura Prochazka

Nika Shakiba

Tiam Heydari

Daniel Aguilar-Hidalgo

Curtis Woodford

Elia Piccinini

David Becerra-Alonso

Alice Vickers

Blaise Louis

Nafees Rahman

Davide Danovi

Mieke Geens

Fiona M Watt

Peter W Zandstra

Affiliations

Soon will be listed here.

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.

Citing Articles

Morphogen-driven differentiation is precluded by physical confinement in human iPSCs spheroids.

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Recapitulation and investigation of human brain development with neural organoids.

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Programming of Multicellular Patterning with Mechano-Chemically Microstructured Cell Niches.

Newman P, Yip Q, Osteil P, Anderson T, Sun J, Kempe D Adv Sci (Weinh). 2023; 10(15):e2204741.

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Synthetic gene circuits for cell state detection and protein tuning in human pluripotent stem cells.

Prochazka L, Michaels Y, Lau C, Jones R, Siu M, Yin T Mol Syst Biol. 2022; 18(11):e10886.

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Kaul H, Werschler N, Jones R, Siu M, Tewary M, Hagner A Stem Cell Reports. 2022; 18(1):377-393.

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