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Feeder-free Derivation of Neural Crest Progenitor Cells from Human Pluripotent Stem Cells
Published on: May 22, 2014
Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation
P M White1, S J Morrison, K Orimoto
1Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.
Neural crest stem cells (NCSCs) from rat sciatic nerves generate fewer neurons and primarily parasympathetic types when transplanted. Their altered BMP2 sensitivity influences neuronal fate, impacting sympathetic versus parasympathetic differentiation.
Area of Science:
- Developmental biology
- Stem cell biology
- Neuroscience
Background:
- Neural crest stem cells (NCSCs) are multipotent cells crucial for development.
- NCSC differentiation is influenced by extrinsic signals and cell-intrinsic properties.
- Understanding factors governing NCSC fate is key to regenerative medicine.
Purpose of the Study:
- To investigate the neurogenic potential and differentiation capacity of rat NCSCs from different developmental stages and origins.
- To determine the role of Bone Morphogenetic Protein 2 (BMP2) signaling in NCSC differentiation towards sympathetic and parasympathetic neuronal fates.
- To explore cell-intrinsic changes in NCSC sensitivity to instructive signals.
Main Methods:
- Prospective isolation of rat NCSCs from E14.5 sciatic nerve and E10.5 neural tube explants.
- Transplantation of NCSCs into chick embryos to assess in vivo neurogenesis.
- In vitro differentiation assays to evaluate neuronal subtype generation.
- Assessment of NCSC sensitivity to varying BMP2 concentrations.
Main Results:
- Sciatic nerve-derived NCSCs generated fewer neurons compared to neural tube-derived NCSCs after transplantation.
- Sciatic nerve NCSCs predominantly differentiated into cholinergic parasympathetic neurons in vivo.
- In vitro, sciatic nerve NCSCs showed reduced sensitivity to BMP2, with cholinergic neuron differentiation occurring at lower BMP2 concentrations than noradrenergic neurons.
- NCSCs maintained multipotency and self-renewal capacity despite altered BMP2 sensitivity.
Conclusions:
- Neural stem cells exhibit cell-intrinsic changes in sensitivity to instructive signals like BMP2.
- The local concentration of BMP2 can determine the sympathetic versus parasympathetic neuronal fate choice.
- These findings offer insights into the plasticity of neural stem cells and their potential for targeted differentiation.
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