Unlocking the Mysteries of Brain Regeneration – Groundbreaking Study Offers New Insight



The axolotl Ambystoma mexicanum is a well-liked pet due to its unique and endearing appearance. Neoteny is the ability of axolotls (pronounced ACK-suh-LAH-tuhl) to never outgrow their larval, juvenile stage. This distinguishes them from other metamorphosing salamanders. It is also known for its capacity to regenerate tissues such as the retina, cornea, and lens in the eye, as well as the brain, spinal cord, tail, skin, limbs, liver, skeletal muscle, heart, upper and lower jaw.

After a brain injury, mammals, including humans, almost never recover the destroyed tissue. On the other hand, some species, including fish and axolotls, may repopulate damaged brain regions with new neurons.

The types of tissue the axolotl can regenerate are depicted in red. Done in 2016 by Debuque and Godwin

The coordination of intricate actions in a manner that is time- and region-specific is required for brain regeneration. BGI and its research partners employed Stereo-seq technology to reconstruct the axolotl brain architecture throughout developmental and regeneration processes at single-cell resolution in a publication that was featured on the Science cover. Better therapies for serious wounds and the ability to regenerate in humans may result from studying the genes and cell types that allow axolotls to renew their brains.
Axolotl samples from six developmental stages and seven regeneration phases were gathered by the research team together with the associated spatiotemporal Stereo-seq data. Among the six developmental phases are:

the first feeding stage following emergence (Stage 44)

the stage of forelimb development (Stage 54)

the stage of hindlimb development (Stage 57)

infant stage

Adulthood

Metamorphosis

Researchers discovered through the systematic study of different cell types at different developmental stages that while early development stage neural stem cells in the VZ region are hard to distinguish between subtypes, from adolescence onwards there are specialized neural stem cell subtypes with spatial regional characteristics, suggesting that different subtypes may have different functions during regeneration.

The final element of the investigation involved the creation of a set of spatial transcriptomic data of telencephalon sections that covered seven stages of injury-induced regeneration. Reactive ependymoglial cells, a new subtype of neural stem cells, started to show up in the location of the wound after 15 days.

After 20 to 30 days, fresh tissue had started to regenerate at the site of the injury. However, the cell type composition was noticeably different from that of the unharmed tissue. Only 60 days after the injury did the cell types and distribution in the affected area resemble those in the unharmed tissue.

The main neural stem cell subtype (reaEGC) involved in this process was created when the quiescent neural stem cell subtypes (wntEGC and sfrpEGC) around the wound were stimulated by injury and then activated and transformed.

What parallels and distinctions exist between the creation of neurons during development and regeneration? Researchers found that the development and regeneration processes follow a similar pattern, starting with neural stem cells and progressing via progenitor cells, immature neurons, and mature neurons.

Axolotl brain development is distributed both spatially and temporally. BGI Genomics, inc.

Researchers compared the molecular characteristics of the two processes and discovered that the formation of neurons during development and regeneration is very similar. This finding suggests that injury causes neural stem cells to change into a rejuvenated state of development to start the regeneration process.

According to Dr. Xiaoyu Wei, the lead author of this study and a senior researcher at BGI-Research, "Our team investigated the critical cell types in the process of axolotl brain regeneration, and followed the changes in its spatial cell lineage." "Stereo-seq has given us a powerful tool to create new research pathways in the biological sciences thanks to the spatiotemporal dynamics of major cell types it has uncovered."

According to the corresponding author, BGI-Director Research's of Life Sciences Xun Xu, "There are numerous self-regenerating organisms in nature, and the processes of regeneration are fairly diverse. Globally dispersed scientists could collaborate more systematically thanks to multi-omics technologies.

By BGI GENOMICS 

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