Neural stem cell engineering: directed differentiation of adult and embryonic stem cells into neurons
Matthew J. Robertson1, Phung Gip2, David V. Schaffer1
1
Department of Chemical Engineering & The Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, 2 Department of Cell and Molecular Biology, University of California, Berkeley, CA
TABLE OF CONTENTS
- 1. Abstract
- 2. Introduction
- 3. Adult neural stem cells and neurogenesis
- 3.1. Hippocampal stem cells
- 3.2. Subventricular zone (SVZ) and olfactory bulb stem cells
- 3.3. Progenitors derived from non-neurogenic regions
- 3.4. Adult neural stem cell engraftment in vivo
- 3.4.1. Hippocampal derived neural stem cells
- 3.4.2. SVZ derived neural stem cells
- 3.4.3. Spinal cord progenitors
- 3.4.4. Cortical derived progenitors
- 3.4.5. Substantia nigra (SN) derived neural progenitors
- 3.5. Inducing neuronal differentiation with microenvironmental signals and genetic manipulation
- 3.5.1. Retinoic acid
- 3.5.2. Morphogens and growth factors
- 3.5.3. Neurotransmitters
- 3.5.4. Genetic manipulation
- 4 Adult and embryonic stem cells
- 5. Embryonic stem cells
- 5.1. Expanding and culturing embryonic stem cells
- 5.2. Embryoid body culture
- 5.3. Inducing neural specification using media supplements and co-culturing with stromal cells
- 5.3.1. Retinoic acid
- 5.3.2. Growth factors and morphogens in the induction of neural differentiation
- 5.3.3. Stromal cell-derived inducing activity (SDIA)
- 5.4. Neuronal-subtype specification
- 5.4.1. Dopaminergic specification
- 5.4.2. Motor neuron specification
- 5.4.3. Other neuronal subtypes
- 5.5. Therapeutic potential of embryonic stem cells in animal models
- 5.5.1. ES cell-derived dopaminergic cells
- 5.5.2. ES cell-derived motor neurons
- 5.5.3. ES cell-derived retinal progenitors
- 6 Conclusion
- 7. Acknowledgement
- 8. References
1. ABSTRACT
Both adult neural stem cells and embryonic stem cells have shown the capacity to differentiation into multiple cell types of the adult nervous system. They will therefore serve as valuable systems for basic investigations of cell fate choice mechanisms, as well as play important future roles in applications ranging from regenerative medicine to drug screening. However, there are significant challenges remaining, including the identification of signaling factors that specify cell fate in the stem cell niche, the analysis of intracellular targets and mechanisms of these extracellular signals, and the development of ex vivo culture systems that can exert efficient control over cell function. This review will discuss progress in the identification of signaling mechanisms and culture systems that regulate neural differentiation, neuronal differentiation, and neuronal subtype specification.
