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Real-time imaging sheds light on the regulation of neural stem cell activation

In all adult vertebrates, neural stem cells can be mobilized to generate new neurons in the brain. However, little is known about these so-called “activation” processes.

Scientists at Institute Pasteur, CNRS, Tel Aviv University collaborate with École Polytechnique and INRAE ​​to successfully 3D visualize neural stem cell activation and spatial and temporal distribution analysis in the adult brain of a zebrafish vertebrate model I ran it on the back.

Their findings show for the first time that the activation events of these cells are coordinated in time and space. In particular, these results may help to better understand the regulatory processes that occur during brain tumor formation. The results of these findings are published in the April 5, 2021 issue of the journal. Cell stem cell.

Stem cells found in many adult organs of vertebrates, including humans, can proliferate and differentiate to produce new functional cells. For example, brain stem cells (neural stem cells) produce new neurons in adulthood. Most often, neural stem cells are in a dormant state known as “quiescent.” Therefore, in order to generate neurons, they must first be activated and then divide. This activation stage is very important. This is a prerequisite for stem cell recruitment and is also important for their survival (overactive cells are quickly depleted) and the location and type of neurons formed.

Within those niches, neural stem cells are activated asynchronously in a random order and return to dormancy, suggesting that these events may be regulated at the cell population level. Scientists in the Zebrafish Neurogenetic Unit of the Institute Pasteur chose zebrafish to test this hypothesis because the adult zebrafish brain contains a large amount of neural stem cells.

In vivo (non-invasive) two-photon imaging of adult fish allowed us to photograph niche stem cells for several weeks and study the activation patterns of each cell in real time in relation to adjacent cells. Spatial statistical analysis and modeling performed in both real-time and long-term computational simulations showed the presence of inhibitory interactions produced by activated cells, delaying activation of other adjacent stem cells by several days. It was.

Scientists have also identified involved molecular pathways known as Notch signaling pathways by administering pharmacological molecules in vivo. Finally, they demonstrated that these interactions enable the generation of stable neurons in time and space.

“This is the first real-time and long-term imaging of the entire neural stem cell population in the adult vertebrate brain. These findings are that the neural stem cell activation event in the vertebrate brain is coordinated in time and within the niche. “Space,” commented Laure Bally-Cuif, a CNRS scientist, lead author of research, and head of the Zebrafish Neurogenetics Unit 1 at the Pasteur Institute. Surprisingly, this study also shows that the stem cells themselves are involved in this coordination. Therefore, this study prompted the emergence of a new concept in which stem cell populations self-organize as a dynamic system that allows spatiotemporal coordination of individual cell behavior.

Such regulation can occur in tumor masses containing cancerous stem cells in which various quiescent or activated stem cells have been observed. Also, such regulation can occur in stem cell populations of other adult organs where stem cells are found in compact niches such as the epithelium.

Link to a video showing stem cells covering one of the adult cerebral hemispheres. Stem cells were monitored for 23 days to analyze their location, activation events, and differentiation. The fish were anesthetized and photographed every 3 days using a two-photon microscope. The dots indicate the center of each cell and the arrows indicate the dividing stem cells: https: // /to see? v =bPZsMz5tsGM


Journal reference:

Dray, N. , et al. (2021) Dynamic spatiotemporal coordination of neural stem cell fate decisions occurs through local feedback in the adult vertebrate brain. Cell stem cell.

Real-time imaging sheds light on the regulation of neural stem cell activation

Source link Real-time imaging sheds light on the regulation of neural stem cell activation

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