In EPIScOPE, we have used emerging technologies, called single-cell transcriptomics and epigenomics, that allows to identify in one single cell which molecules the cell has available. We have used this technology to establish a comprehensive library how oligodendrocytes are different during normal development and in MS.
In one study published in 2018 in Developmental Cell, we found that oligodendrocytes forget their origins throughout their life, unlike other nerve cells. Oligodendrocytes originate in different locations in the brain and spinal cord. When their ancestor cells are first generated during the early stages of life, they have different properties depending on the region they come from. We found that the ancestor cells of oligodendrocytes are different depending on which region of the brain they come from. These differences are later lost, and the cells become very similar independently of where they end up.
In another study published in Nature Medicine in 2018, we found that a subset of oligodendrocytes and their progenitor cells in a mouse model of MS have much in common with the immune cells. Among other properties, they can take part in the clearing away of the myelin that is damaged by the disease. Oligodendrocyte progenitor cells can also communicate with the immune cells and make them change their behaviour. We observed that some genes that have been identified as those that cause a susceptibility to MS are active (expressed) in oligodendrocytes and their progenitors. Thus, our experiments suggest that these cells have a significant role to play either in the onset of the disease or in the disease process.
We also mapped oligodendrocytes in human samples from post-mortem brains of MS patients, in collaboration with Prof. Anna Williams and Charles ffrench-Constant at University of Edinburgh, and the pharmaceutical company Roche in Basel. We found changes in different oligodendrocyte subpopulations in MS, suggesting a more complex role of these cells in the pathology of the disease, but also in regeneration of new cells. For instance, we found that oligodendrocyte precursor cells, which are thought to have a crucial role in relapsing-remitting MS to restore myelin, are depleted in the progressive disease. This paper was recently published in Nature, in January 2019.
Even though all cells in our bodies contain exactly the same genetic information written in DNA, they read and execute this information differently. For example, a neuron in the brain reads the DNA differently than a skin cell or a fat cell. Histones are tiny proteins that bind to DNA and hold information that can help turn on or off individual genes. We developed a technique that makes it possible to examine how different versions of histones bind to the genome in tens of thousands of individual cells simultanously. The technique was applied to the mouse brain and can be used to study epigenetics at a single-cell level in other complex tissues. The study was published in Nature Biotechnology in 2021.
We will now continue to investigate and modulate the activity of the identified molecules in oligodendrocytes and determine if we can alter the character of the cells and their capacity to mature and produce myelin, or modulate the immune system.
