DLX2 Reprograms Astrocytes to Produce Neurons

One of the potential paths to regenerative therapies for the aging brain is to reprogram supporting cells to produce neurons that can then integrate into existing neural networks, a supplemental form of neurogenesis. One has to be a little cautious in reading new research on this topic, given that some past work has proven to be a dead end, the victim of difficulties in determining exactly what is going on inside the brain. Nonetheless, a number of different groups are pursuing a number of different possibilities; one might hope that at least one approach will bear fruit. The example here is at a comparatively early stage of discovery.

During development, mammalian stem cells readily proliferate to produce neurons throughout the brain and cells - called glia - that help support them. Glia help maintain optimal brain function by performing essential jobs like cleaning up waste and insulating nerve fibers. However, the mature brain largely loses that stem cell capacity. Only two small regenerative zones, or niches, remain in the adult brain, leaving it with extremely limited capacity to heal itself following injury or disease.

Looking for a way to spur this "multipotent" regeneration, researchers used a genetic engineering technique in adult mouse brains to induce astrocytes, a subset of glia, to produce different transcription factors, proteins pivotal for controlling cell identity. These experiments showed that a single transcription factor - a protein known as DLX2 - appeared to reprogram astrocytes into neural stem-like cells capable of producing neurons and multiple subtypes of glial cells.

The researchers confirmed these findings both using a technique called lineage tracing, in which they followed progeny of the altered astrocytes as they multiplied, as well as marker analysis that showed that these new cells had the expected identities of neurons or glia. Researchers suggest that DLX2 might someday be used as a tool to treat traumatic brain injuries, strokes, and degenerative conditions .

Link: https://www.utsouthwestern.edu/newsroom/articles/year-2022/single-protein-prompts-mature-brain-cells.html

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