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Cited by 158

The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.

A stepwise model of Reaction-Diffusion and Positional-Information governs self-organized human peri-gastrulation-like patterning

Open access
Tewary, Mukul, Ostblom, Joel, Prochazka, Laura, Zulueta-Coarasa, Teresa, Shakiba, Nika, Fernandez-Gonzalez, Rodrigo, Zandstra, Peter W.·2017·Development

Abstract

How position-dependent cell fate acquisition occurs during embryogenesis is a central question in developmental biology. To study this process, we developed a defined, high-throughput assay to induce peri-gastrulation-associated patterning in geometrically-confined human pluripotent stem cell (hPSC) colonies. We observed that, upon BMP4 treatment, phosphorylated SMAD1 (pSMAD1) activity in the colonies organized into a radial gradient. We developed a Reaction-Diffusion (RD) based computational model and observed that the self-organization of pSMAD1 signaling was consistent with the RD principle. Consequent fate acquisition occurred as a function of both pSMAD1 signaling strength and duration of induction – consistent with the Positional-Information (PI) paradigm. We propose that the self-organized peri-gastrulation-like fate patterning in BMP4 treated geometrically-confined hPSC colonies arises via a stepwise model of RD, and PI. This two-step model predicted experimental responses to perturbations of key parameters such as colony size, and BMP4 dose. Furthermore, it also predicted experimental conditions that resulted in RD-like periodic patterning in large hPSC colonies, and rescued peri-gastrulation-like patterning in colony sizes previously thought to be reticent to this behaviour.

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Crossref · 10.1242/dev.149658

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Metadata

Authors
Tewary, M., Ostblom, J., Prochazka, L., Zulueta-Coarasa, T., Shakiba, N., Fernandez-Gonzalez, R., & Zandstra, P. W.
Venue
Development
Published
2017-01-01
Volume
144
Issue
23
Pages
4298-4312
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2751928832
Cited by
158
References
7
FWCI
6.89
Type
journal article
Language
en
Open access
hybrid

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