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Different Mixed Astrocyte Populations Derived from Embryonic Stem Cells Have Variable Neuronal Growth Support
Russell E Thompson1,2, Allison Lake3,4, Peter Kenny2
11 Department of Biomedical Engineering, Washington University in St. Louis , St. Louis, Missouri.
Stem Cells and Development
|August 31, 2017
Summary
Central nervous system injury recovery depends on astrocyte phenotype. Protoplasmic astrocyte substrates promote neurite growth, while fibrous astrocyte substrates inhibit it, impacting spinal cord regeneration.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Cell Biology
Background:
- Central nervous system (CNS) injury often results in functional impairment due to glial scar formation, traditionally viewed as inhibitory.
- Recent research suggests astrocytes, the main glial scar cells, can support spinal cord regeneration depending on their specific phenotype.
Purpose of the Study:
- To investigate the differential effects of distinct astrocyte subtypes on neuronal growth.
- To characterize the extracellular matrix (ECM) composition of different astrocyte-derived substrates and its impact on neurite extension.
Main Methods:
- Derived mixed astrocyte populations (fibrous and protoplasmic) from mouse embryonic stem cells (mESCs).
- Assessed motoneuron and V2a interneuron growth on live astrocyte cultures, freeze-lysed cultures, and decellularized astrocyte-derived ECM.
- Analyzed ECM protein composition and performed gene knockdown experiments.
Main Results:
- Neurons extended significantly longer neurites on protoplasmic astrocyte-derived substrates and ECM compared to fibrous-derived substrates.
- Protoplasmic ECM was enriched in axon growth-promoting proteins, while fibrous ECM contained higher levels of axon growth inhibitors.
- Knockdown of specific proteins (spondin-1, laminin α5, γ1) altered neurite growth on respective substrates.
Conclusions:
- Astrocyte subtype and its derived ECM play a critical role in supporting or inhibiting neuronal regeneration after CNS injury.
- Scalable production of specific astrocyte populations enables further study into astrocyte heterogeneity and functional importance in recovery.
