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Engineering artificial signaling centers to polarize embryoid body differentiation
Dorthe R Petersen1, Carsten Gustavsen, Søren R Lindskog
1Department of Stem Cell Biology, Hagedorn Research Institute, Gentofte, Denmark.
Stem Cells and Development
|October 1, 2011
Summary
Embryonic stem cells can be guided to differentiate in a controlled manner. Engineered fibroblasts create localized signaling centers, directing stem cell organization and differentiation for tissue engineering applications.
Area of Science:
- Developmental biology
- Stem cell biology
- Tissue engineering
Background:
- Embryonic stem (ES) cells differentiate through self-organization, driven by Wnt signaling.
- Wnt signaling initially localized in ES cell aggregates expands, leading to mesendodermal progenitor differentiation.
- Disorganized differentiation occurs due to a lack of positional information in differentiating ES cell aggregates.
Purpose of the Study:
- To investigate methods for controlling the initiation site of differentiation in ES cell aggregates.
- To explore the use of engineered fibroblasts as localized signaling sources to guide ES cell differentiation.
Main Methods:
- Formation of composite aggregates using ES cells and engineered fibroblasts.
- Engineering fibroblasts to express cadherins for positional control within aggregates.
- Engineering fibroblasts to express Wnt agonists or antagonists to localize signaling.
Main Results:
- Fibroblasts positioned at a discrete pole within composite aggregates.
- Localized Wnt signaling from engineered fibroblasts polarized the differentiating ES cell aggregates.
- Exogenous signaling sources controlled the site of differentiation initiation.
Conclusions:
- Engineered fibroblasts can serve as localized signaling centers to control ES cell aggregate differentiation.
- Cell adhesion molecules can direct the morphology and differentiation of stem cell aggregates.
- This approach holds promise for applications in tissue engineering and developmental biology research.
