Unknown

Dataset Information

0

A stepwise model of reaction-diffusion and positional information governs self-organized human peri-gastrulation-like patterning.


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 followed by 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 behavior.

SUBMITTER: Tewary M 

PROVIDER: S-EPMC5769627 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

A stepwise model of reaction-diffusion and positional information governs self-organized human peri-gastrulation-like patterning.

Tewary Mukul M   Ostblom Joel J   Prochazka Laura L   Zulueta-Coarasa Teresa T   Shakiba Nika N   Fernandez-Gonzalez Rodrigo R   Zandstra Peter W PW  

Development (Cambridge, England) 20170904 23


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 mo  ...[more]

Similar Datasets

| S-EPMC10266723 | biostudies-literature
| S-EPMC6070580 | biostudies-literature
| S-EPMC9523701 | biostudies-literature
| S-EPMC6822778 | biostudies-literature
| S-EPMC5471612 | biostudies-literature
| S-EPMC3525670 | biostudies-literature
| S-EPMC3533082 | biostudies-literature
| S-EPMC8325926 | biostudies-literature
| S-EPMC7648603 | biostudies-literature
| S-EPMC5430225 | biostudies-literature