How does an injured brain recover on its own? Science: Scientists successfully constructed the world's first spatio-temporal atlas of brain regeneration

On September 2, 2022, BGI Life Sciences Research Institute, together with the team of Professor Fei Jifeng of Guangdong Provincial People's Hospital and the team of Professor Chen Liang of Wuhan University, published a research paper entitled "Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration" in science, a top international academic journal
。
The study mapped the first spatial-temporal atlas of salamander brain regeneration, which is also the world's first spatio-temporal atlas
of brain regeneration.
Based on BGI spatiotemporal omics Stereo-seq technology, the research team systematically analyzed and compared the development and regeneration process of salamander brains, found the key neural stem cell subsets in the regeneration process of salamander brains, depicted the process of reconstructing and damaging neurons in such stem cell subsets, and also found that brain regeneration and development process have certain similarities, providing a boost for cognitive brain structure and development process, and providing a new direction
for regenerative medicine research and treatment of the nervous system.

So far, in just half a year, BGI's achievements related to spatiotemology and single-cell technology have been published in three top journals of Cell, Nature and Science for four consecutive times, achieving a grand slam
.
The Mexican blunt-mouthed salamander used in this study is a type of salamander, also known as a hexagonal dinosaur, which has a unique, cute appearance and strong regenerative ability
.

If a human is unfortunate enough to have a limb amputated, the wound will heal slowly, but no new limbs
will grow.

If an organ is diseased or damaged, it is necessary to rely on organ transplantation for treatment
.

Miraculously, the Mexican blunt-mouthed salamander can not only regenerate organs such as limbs, tail, eyes, skin and liver, but also regenerate the brain, which is why scientists are used as important model organisms to study the problem
of regeneration.
The paper appears on the cover
of this issue of Science: "In addition to its powerful regenerative abilities, salamanders are more evolutionarily superior to other telesophageal fish and have a higher degree of similarity
to mammalian brain structures.
"
At the same time, its gene coding sequence is extremely similar to that of humans, studying the initiation mechanism of salamander brain regeneration, and discovering the key genes in it, or will provide important guidance
for the repair of human nervous system damage or degenerative diseases.

Dr.
Gu Ying, co-corresponding author of the paper and Hangzhou Huada Life Science Research Institute, said
.
In this study, the research team composed of BGI and others first constructed a spatio-temporal map of salamander brain development covering 6 developmental important periods, showing the molecular characteristics and spatial distribution dynamic changes of various types of neurons, and found that salamander brains began to specialize subtypes
of neural stem cells with spatial regional characteristics from adolescence.
To study the regeneration process after salamander brain injury, the team performed mechanical damage surgery on the cortical area of the salamander brain and analyzed brain samples
from 7 time points of regeneration (days 2, 5, 10, 15, 20, 30 and 60 after injury).

The spatiotemporal data showed that a new subset of neural stem cells appeared in the wound area early in the injury, and this important group of cells was transformed from other subpopulations of neural stem cells near the injury area after being stimulated by the injury, and neurons were regenerated in the subsequent regeneration process to fill the neuronal deletions
at the injury site.

In addition, although the wound begins to be gradually filled with nascent tissue at an early stage, it is not until day 60 after injury that the cell type and spatial distribution of the injured area are observed on the space-time map to return to the state of
the uninjured side.
By comparing the neuronal formation process of the salamander brain development and regeneration process, the researchers found that this process is highly similar to the regeneration and development process, suggesting that brain damage may induce the reverse transformation of salamander neural stem cells back to the youthful state of the developmental period to initiate the regeneration process
.
Spatial-temporal atlas of salamander brain regeneration"This study is mainly based on the spatiotemporal omics technology Stereo-seq independently developed by BGI, which achieves nano-level cell resolution, combined with the advantages of large salamander cells, so that researchers can analyze the important cell types in the process of salamander brain regeneration in spatiotemporal single-cell resolution, and track the spatial trajectory
of their cell lineage changes.

The first author of the paper, Dr.
Wei Xiaoyu of Hangzhou Huada Life Science Research Institute, introduced.

"The construction of the spatial and temporal cell map of axolotls brain development and regeneration is of great significance for us to understand the important life process of brain regeneration, the brain structure of amphibians and the evolution of brain structure, providing a new direction for us to find effective clinical treatment methods, promote self-repair and regeneration of human tissues and organs, and provide valuable data resources
for the study of species evolution.
"
Xu Xun, co-corresponding author of the paper and president of the BGI Life Sciences Research Institute, said, "In the future, we will also explore the development and regeneration process of more organs and more species through spatiotem-time multi-omics technology, find the key regulatory mechanisms in the regeneration process, and help the development of
human regenerative medicine.
"
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