The influence of lipid droplets on brain stem cells 

In this blog, we will discuss how lipid droplets can influence the stem cells in the brain.

Stem cells are undifferentiated cells that can develop in different types of cells. In the brain, neural stem/progenitor cells (NSPCs) have the potential to develop into neurons and other brain cells.

Lipid metabolism influences the activity of NSPCs. The breakdown of lipids stimulates quiescence, while the buildup of lipids promotes proliferation. Quiescence is a reversible cell state in which cells do not divide but retain the ability to re-enter a proliferative state. Proliferation indicates that a cell divides and in the case of a stem cell, daughter cells can differentiate or become a new stem cell.  

Lipids are stored in specific organelles, which are called lipid droplets (LDs). However, the role of LDs in NSPCs remained unknown.

In this study, using multiple techniques, including single-cell RNA sequencing, it was shown that LDs influence the behaviour of adult mouse NSPCs. This research was published in Nature Communications in December 2021.

Instructive role of LDs in NSPC behavior

This research shows that adult mouse NPSCs contain abundant LDs. Furthermore, the accumulation of LDs is altered upon fate changes including quiescence and proliferation. The proliferation of NSPCs is influenced by the number of LDs, inhibition of LD buildup, breakdown of LDs, and asymmetric distribution of LDs over daughter cells during cell division. In addition, NSPCs with a high number of LDs have an increased metabolic activity and capacity. Therefore, it can be concluded that LDs are important in determining the behaviour of NSPCs.

Single-cell sequencing: how do high and low LD NSPCs differ at gene expression level?

In this study, single-cell RNA sequencing was performed at Single Cell Discoveries to analyze gene expression patterns in NSPCs with either a high or low number of LDs. For this, the SORT-seq platform was used which resulted in a gene expression dataset of 304 cells.

Analysis of the gene expression dataset showed that a few genes were upregulated in high LD NSPCs compared to low LD NSPCs. One of these genes promotes neural stem cell maintenance and proliferation. Other genes are downregulated in high LD NSPCs compared to low LD NSPCs, including a gene important for neurogenesis and neuronal maturation. These results indicate that NSPCs with a high number of LDs are slightly more stem cell-like compared to low LD NSPCs.

This data contributes to our understanding of the role of lipid metabolism in stem cells and also increase the fundamental knowledge of stem cell functioning. Future research can uncover if and how this knowledge on lipid organelles and metabolism in NSPCs can contribute to translational research.

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