mexican axolotl.
All pictures in this column are provided by the BGI Life Sciences Research Institute
Spatiotemporal map of brain regeneration in the Mexican axolotl.
It is difficult for the human brain to recover on its own after being injured, but the Mexican axolotl can not only regenerate its limbs, tail, eyes, skin, liver and other organs, it can even regenerate its brain.
Why can Mexican axolotls regenerate their brains? What key changes occurred during this process? What important cells are involved? What functions do they perform?
In order to answer the above questions, a research team composed of scientists from 18 units in three countries, including BGI Life Sciences Research Institute, Guangdong Provincial People's Hospital , analyzed and compared the brain development and regeneration process of Mexican axolotl, and constructed Developed the world's first spatiotemporal map of brain regeneration in the Mexican axolotl.
Through research, scientists have found the key neural stem cell subpopulation in the brain regeneration process of the Mexican axolotl, and described the process of this type of stem cell subpopulation reconstructing damaged neurons. They also found that its brain regeneration and development processes have certain similarities. properties, provide assistance for cognitive brain structure and development processes, and provide new directions for regenerative medicine research and treatment of nervous system . On September 2, the relevant results were published in the top international academic journal "Science" in the form of back-to-back cover articles. Relevant research results have passed ethical review and strictly follow corresponding regulations and ethical guidelines. The Mexican axolotl used in the experiment was cultured in the laboratory.
Key neural stem cell subsets
Reconstruction Brain damage Neurons
The Mexican axolotl is a type of amphibian of the genus Ambystoma of the suborder Salamanders . The adult body length is 20-25 cm, with a large head and a large mouth. There are six feathery pink external gills on both sides of the flat head, which resemble the horns of a dragon, so it is also called the " hexagonal dinosaur ". It has strong regenerative ability and is used by scientists as an important model organism to study regeneration-related problems.
To understand how the Mexican axolotl's brain regenerates, scientists first need to understand how the brain develops. It is reported that scientists used the spatio-temporal omics technology Stereo-seq, which can be called an ultra-wide-angle tens of billions of pixels "life camera", to take photos at six important stages of the brain development of the Mexican axolotl. This set of photos constitutes Spatiotemporal map of brain development in Ambystoma mexicana.
Through the spatiotemporal map, scientists can see the dynamic changes in the molecular characteristics and spatial distribution of various types of neurons during the development of the Mexican axolotl brain. The results showed that the brain of Ambystoma mexicana begins to specialize in subtypes of neural stem cells with spatial and regional characteristics starting in adolescence.
It is reported that neural stem cells are mother cells with the ability to divide and self-renew, and play an important role in the repair of neurological diseases.
What is the process of brain regeneration after damage? The research team performed mechanical injury surgery on the cortical area of the Mexican axolotl brain, and used the spatiotemporal omics technology Stereo-seq to take pictures of brain samples on days 2, 5, 10, 15, 20, 30 and 60 days after the injury. , obtaining an atlas of brain regeneration at various time points, completely recording the process of the Mexican axolotl brain from damage to regeneration and repair.
It is understood that brain regeneration requires the coordination of complex reactions in a time- and region-specific manner. Identifying the cells and molecules involved in this process will advance scientists' understanding of brain regeneration.
By comparing the regeneration photos in 7 periods with the wound status during the process, the research team found that new neural stem cell subpopulations appeared in the wound area in the early stage of injury. This important group of cells was composed of other neural stem cell subpopulations near the injured area. It is activated and transformed after being stimulated by damage. "During the subsequent process of injury repair, we saw that this important subset of activated neural stem cells can proliferate and gradually differentiate. They first differentiate into intermediate neural progenitor cells, and then differentiate into immature neurons. , and finally mature neurons are formed. Through this differentiation process, they can fill in the loss of neurons caused by the injury, and finally achieve nerve regeneration in the brain after injury."The co-corresponding author of the paper , Dr. Gu Ying of the Hangzhou BGI Life Sciences Institute, said.
In addition, although the wound began to be gradually filled with new tissue in the early stages of repair, it was not until the 60th day after the injury that the photos showed The cell types and spatial distribution in the damaged area returned to the state on the undamaged side.
Nanoscale spatiotemporal omics technology
enables in-situ cell observation
Due to the huge genome of Ambystoma mexicanus, Scientists need to conduct a large number of gene sequencing and massive data analysis. The development of
technology makes the advancement of this research possible. "This research is mainly based on the spatiotemporal omics technology Stereo-seq independently developed by BGI, which reaches the nanometer level. Cellular resolution, combined with the advantage of the large cell size of Ambystoma mexicana, allows researchers to analyze important cell types in the brain regeneration process of Ambystoma mexicanus at spatiotemporal single-cell resolution, and track the spatial trajectory of their cell lineage changes. . "The first author of the paper, Dr. Wei Xiaoyu from BGI Life Sciences Institute in Hangzhou, said.
Compared with past microscopes and sequencing technologies, spatio-temporal omics technology can observe cell morphology and tissue morphology at the same time, and can also observe at the molecular level Comprehensive detection of gene transcriptome enables "Therefore, we used spatiotemporal omics technology to study the process of brain regeneration in Mexican axolotl, and realized the key stem cells that are actually involved in regeneration near the injury site. In-situ observation and analysis of dynamic changes in . " Fei Jifeng, corresponding author of the article and professor at Guangdong Provincial People's Hospital, said.
"For example, on days 2 to 15 after brain injury in Mexican axolotls, a type of highly expressed microglia and a type of activated neural stem cells were found. The subpopulation is highly enriched, and the former may be related to the immune response after injury, while the latter may promote the regeneration process. "Wei Xiaoyu said.
"This also reminds us that brain damage in Mexican axolotl may induce the damaged area to restart the development program. "Gu Ying said.
Through sophisticated technology, the complete observation of the brain development and brain injury of the Mexican axolotl at 7 periods, the researchers found that the neuron formation process of the brain development and regeneration of the Mexican axolotl is highly similar.
or Provide guidance for the repair of human nervous system damage
or degenerative diseases
"The release of the spatiotemporal map of brain regeneration in the Mexican axolotl is an important progress in the field of neuronal injury regeneration. "Li Chengyu, a researcher at the Center for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, said.
chose the Mexican axolotl for research not just because of its strong regenerative ability. Gu Ying said: "The Mexican axolotl is evolutionarily different from other hard bones. Fish are more advanced and have a higher degree of similarity with mammalian brain structures. At the same time, its gene coding sequence is very similar to that of humans. Studying the initiation mechanism of brain regeneration in Mexican axolotl and discovering the key genes may provide important guidance for the repair of human nervous system damage or degenerative diseases. "
The key gene in the brain regeneration process of the Mexican axolotl also exists in the human gene sequence. So why does it not play the same regenerative role as in the Mexican axolotl's brain? This may be the next topic for scientists to study .
"Spatiotemporal cells of brain development and regeneration in Ambystoma mexicana" The construction of the map is of great significance to our understanding of the brain structure and the evolution of brain structure in amphibians. It provides a new direction for us to find effective clinical treatments and promote the self-repair and regeneration of human tissues and organs. It also provides new directions for species. Evolutionary research provides a valuable data resource. "Xu Xun, co-corresponding author of the paper and dean of the BGI Institute of Life Sciences, said.
In the future, the BGI Institute of Life Sciences will also use spatiotemporal multi-omics technology to explore the development and development of more organs and more species. Regeneration process, find the key regulatory mechanisms in the regeneration process, and help the development of human regenerative medicine. "For example, in the direction of regeneration-related research, we are also conducting research on other organs of the salamander , such as the spinal cord and limbs.Through damage studies on multiple organs, we hope to find out some common regulatory mechanisms and systemic response mechanisms for salamander regeneration. " Gu Ying said.
In addition to axolotls, researchers are also conducting regeneration-related research on other species, such as planaria , some fish, etc. "The experimental results will also be compared with those of mice, primates By comparing damage repair, we hope to find the reason why the damage repair ability of species gradually decreases during the evolution process, and also hope to find some mechanisms and targets that can improve the damage repair ability of mammals and even humans. " Gu Ying said.
More importantly, for tumors, heart diseases, infectious diseases, etc., scientists have applied spatiotemporal omics tools to explore the pathogenic mechanisms and intervention mechanisms of diseases, so as to provide guidance for future medical diagnosis and treatment. Provide more clues
Nanfang Daily reporter Zhang Xiujuan
Coordinator: Zhang Zhichao
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