What Mechanisms Distinguish Astrocytes from Neural Stem Cells?
Neural stem cells play a crucial role in generating new neurons in the brain, aiding in memory and learning processes, and even contributing to the brain’s limited capacity for regeneration. On the other hand, astrocytes provide vital support to brain tissue’s structure and metabolism. Despite sharing lineage and biochemical similarities, these two cell types exhibit vastly different functionalities. Understanding the mechanisms behind this contrast may lead to the generation of more neural stem cells from astrocytes, potentially aiding in brain function restoration in aging individuals through increased neuron supply.
Astrocytes are predominantly found in the mammalian brain, offering structural and metabolic support to neurons, regulating synapses, and responding reactively to injury and disease. Interestingly, a subset of astrocytes in specific brain areas exhibits stem cell-like properties, generating neuronal and glial progeny, and are known as neural stem cells. While common astrocytes and quiescent stem cells share similar transcriptomes, their functions differ significantly. The molecular encoding of stem cell activity remains a mystery.
This study delves into the transcriptome, chromatin accessibility, and methylome of neural stem cells, astrocytes from various brain regions, and their responses to ischemic injury in adult mice. Unique methylation patterns associated with astrocytic and stem cell functions were identified, revealing the role of methylation in mediating stem cell activity through gene regulation. Notably, ischemic brain injury prompted striatal astrocytes to adopt stem cell qualities through methylome reprogramming, contingent on the presence of the de novo methyltransferase DNMT3A. Manipulating DNA methylation presents a potential therapeutic strategy for repairing nervous system disorders or combating cancer.
