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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Cripto signaling in differentiating embryonic stem cells
Gabriella Minchiotti1, Silvia Parisi, M Graziella Persico
1Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, Naples, Italy.
Abstract:
Embryonic stem (ES) cells have been suggested as candidate therapeutic tools for regenerative medicine approaches. In this scenario, great efforts are made to define protocols to preferentially direct ES cells toward a defined cell type. To this end, it becomes crucial to characterize the molecular mechanisms as well as the signaling pathways implicated in ES cell differentiation. Findings highlight a key role of cripto, the founding member of a new class of extracellular factors, called EGF-CFC. Indeed, Cripto signaling is strictly required in an early acting window to negatively regulate neural differentiation and to permit differentiation of ES cells to cardiac fate. The protocols defined in this chapter allow preferential direction of ES cell differentiation as embryoid bodies toward either cardiomyocytes or neurons. Although referred to as modulation of Cripto signaling, these methods build the basis for the use of other classes of secreted molecules to control ES cell differentiation.
Insights
Embryonic stem cells can be directed to become heart cells or neurons. Cripto signaling is crucial for this process, regulating differentiation pathways for regenerative medicine applications.
Area of Science:
- Developmental biology
- Stem cell biology
- Regenerative medicine
Background:
- Embryonic stem (ES) cells hold therapeutic potential for regenerative medicine.
- Directing ES cell differentiation towards specific cell types is critical for therapeutic applications.
- Understanding molecular mechanisms and signaling pathways governing ES cell differentiation is essential.
Purpose of the Study:
- To define protocols for preferential differentiation of ES cells into specific lineages.
- To investigate the role of Cripto signaling in regulating ES cell differentiation.
- To establish methods for controlling ES cell differentiation using secreted molecules.
Main Methods:
- Development of protocols for directing ES cell differentiation into cardiomyocytes and neurons.
- Utilizing embryoid body formation as a model system.
- Modulating Cripto signaling pathways to influence differentiation outcomes.
Main Results:
- Cripto signaling plays a key role in early differentiation windows.
- Cripto signaling negatively regulates neural differentiation.
- Cripto signaling is required for ES cell differentiation into cardiac fate.
Conclusions:
- Protocols enabling preferential differentiation of ES cells into cardiomyocytes or neurons have been established.
- Cripto signaling is a critical regulator of ES cell differentiation, impacting cardiac and neural fates.
- The presented methods, based on Cripto signaling modulation, provide a foundation for using secreted factors to control stem cell differentiation.
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