Science blockbuster! Chinese scientists released the world's first "brain regeneration map"!

Brain regeneration requires coordinating complex responses
in time- and region-specific ways.

Identifying the cell types and molecules involved in this process will advance our understanding of brain regeneration and provide potential targets for regenerative medicine research
.

However, progress in this area has been hampered
by the limited regenerative capacity of the mammalian brain and the incomplete understanding of the mechanisms of the regenerative process at the cellular and molecular levels.
The Mexican salamander (axolotl, scientific name Ambistoma mexicanum) can regenerate damaged appendages and multiple internal organs, including the brain
.

Thus, the Mexican salamander can serve as a model
for studying brain regeneration.
If scientists are to understand the mechanisms by which the brain regenerates, they need research tools that enable large-scale data acquisition and analysis to simultaneously decode complex cellular and molecular responses
.

In their view, comparing brain regeneration and developmental processes also helps to provide new insights into
the nature of brain regeneration.
In a new study, researchers from research institutions such as BGI, Guangdong Academy of Medical Sciences, Wuhan University, South China Normal University and the University of Chinese Academy of Sciences cut off a small portion of the lateral cerebral cortex region of the left end of the salamander in Mexico and collected tissue samples
from multiple stages of the regeneration process.

At the same time, they collected tissue samples
of the Mexican salamander telencephalon at multiple stages of development.

They then used high-definition and large-field Stereo-seq (spatial enhanced resolution omics sequencing) technique to generate single-cell resolution spatial transcriptomics data
from slices covering both hemispheres of the Mexican salamander telencephalon.

Cell type annotation, cell spatial distribution, gene activity dynamics, and cell state transitions were analyzed, and the mechanism of injury-induced regeneration was studied
compared with these cellular properties during development 。 The findings were published in the September 2, 2022 issue of the journal Science, "Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration.
"

By using Stereo-seq, the authors produced a set of spatial transcriptome data covering telencephalic slices covering six developmental stages and seven injury-induced regeneration stages
.

These single-cell resolution data allowed them to identify 33 cell types present during development and 28 cell types involved in regeneration, including different types of excitatory and inhibitory neurons, as well as several ependymoglia cell subtypes
.
In terms of development, their data reveal that an original type of ependymal glial cells may produce three adult ependymal glial cell subsets that are distributed in different regions of the ventricular region, with different molecular characteristics and potential functions
.
In terms of regeneration, they found a subset of ependymal glial cells that may have originated from locally resident ependymal glial cells
activated by injury.

This population of progenitor cells may then proliferate to cover the wound area, and then replenish the lost neurons by transitioning to the state of intermediate progenitor cells, immature neurons, and eventually mature neurons
.
When comparing the cellular and molecular dynamics of the Mexican salamander telencephalon between development and regeneration, they found that injury-induced ependymal glial cells were similar
to developmentally specific ePEN GLGs in terms of their transcriptome status.

They also observed that the regeneration of the Mexican salamander telencephalon exhibited similar neurogenesis patterns to during development in terms of molecular cascade and potential cell lineage conversion, suggesting that brain regeneration partially reproduced developmental processes
.
Development and regeneration of the Mexican salamander telencephalon
.

Image from Science, 2022, doi:10.
1126/science.
abp9444
In summary, these spatial transcriptome data highlight the cellular and molecular characteristics
of the Mexican salamander telencephalon during development and during regeneration caused by injury.

Further characterization of ependymal glial cell activation and functional regulation may yield insights
into improving the regenerative capacity of the mammalian brain.

The Mexican salamander obtained by the authors --- a single-cell spatial transcriptome of a tetrapod --- telencephalon also provide useful data
for further study of developmental, regenerative, and evolutionary brain biology.

All data is available
in an interactive database (https://db.
cngb.
org/stomics/artista).
。 References: Xiaoyu Wei et al.
Single-cell Stereo-seq reveals induced progenitor cells involved in axolotl brain regeneration.
Science, 2022, doi:10.
1126/science.
abp9444.

Source | Bio Valley Editing | Swagpp

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