A stepwise model of reaction-diffusion and positional information governs self-organized human peri-gastrulation-like patterning
| Autor: | Laura Prochazka, Nika Shakiba, Teresa Zulueta-Coarasa, Rodrigo Fernandez-Gonzalez, Joel Ostblom, Mukul Tewary, Peter W. Zandstra |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pluripotent Stem Cells Body Patterning Nodal Protein Cellular differentiation Human Development Morphogenesis Human gastrulation Bone Morphogenetic Protein 4 Cell fate determination Biology Models Biological Smad1 Protein Colony-Forming Units Assay 03 medical and health sciences Humans Reaction-diffusion RNA Small Interfering Induced pluripotent stem cell Molecular Biology Cells Cultured Ecology Gastrulation Developmental organoids Cell Differentiation Cell biology High-Throughput Screening Assays 030104 developmental biology Bone morphogenetic protein 4 Positional information Carrier Proteins Developmental biology Developmental Biology Signal Transduction |
| Zdroj: | Development (Cambridge, England) |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | 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. Summary: A high-throughput in vitro system allowing the induction of peri-gastrulation-like fates in geometrically confined hPSC colonies reveals that a two-step process underlies the observed self-organization and subsequent fate acquisition. |
| Databáze: | OpenAIRE |
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