Different Mixed Astrocyte Populations Derived from Embryonic Stem Cells Have Variable Neuronal Growth Support Capacities

Central nervous system (CNS) injuries often result in functional impairment due to the formation of an inhibitory glial scar, which hinders regeneration. Astrocytes, the main cells in the glial scar, were once thought to be primarily inhibitory after injury. However, recent studies suggest that some astrocytes are necessary for spinal cord regeneration, and their roles depend on their specific type. In this study, the researchers created two mixed populations of astrocytes from mouse embryonic stem cells (mESCs), primarily containing either fibrous or protoplasmic astrocytes. They examined how motoneurons and V2a interneurons grew on these astrocyte cultures, both live and after being processed. The study found neurons extended longer neurites on protoplasmic-derived substrates than fibrous-derived substrates. The extracellular matrix (ECM) proteins produced by these astrocytes were analyzed and compared to in vivo astrocyte expression profiles. The ECM from the stem cell-derived astrocytes was found to be rich in astrocyte-specific proteins. Protoplasmic ECM contained more axon growth-promoting proteins, while fibrous ECM had more proteins that inhibit axon growth. These findings suggest that different astrocyte types have distinct effects on neuronal growth.

• 1
  Motoneurons and V2a interneurons extended significantly longer neurites on substrates derived from protoplasmic astrocytes compared to those from fibrous astrocytes.
• 2
  Protoplasmic astrocyte-derived ECM contained significantly higher levels of axon growth-promoting proteins, while fibrous astrocyte-derived ECM had significantly higher levels of proteins that inhibit axon growth.
• 3
  Knockdown of spondin-1, an axon growth-inhibitory protein, improved neurite growth on fibrous ECM, while knockdown of laminin a5 and g1, axon growth-promoting proteins, decreased neurite growth on protoplasmic ECM.