Unexpected Diversity of Crucial Brain Cells Discovered in MS Mouse Study

Discovery of an unexpected diversity of oligodendrocytes in mice could lead to new insights into mechanisms of degeneration and regeneration in multiple sclerosis and other diseases where myelin is lost.

Oligodendrocytes, a type of brain cell that plays a crucial role in diseases such as MS, are more diverse than have previously been thought, according to a new study by researchers at Karolinska Institutet in Sweden.

The findings, published in the journal Science¹, are expected to help increase an understanding of diseases in which these cells are affected and possibly provide clues to future treatment strategies.

The researchers, led by Dr. Gonçalo Castelo-Branco and Dr. Sten Linnarsson, used the recently developed technique of single-cell RNA sequencing. This method allows investigators to get a snapshot of gene activity in individual cells. In this way, they could reveal differences between cells that may not be visible using classical methods.

They analyzed more than 5,000 oligodendrocytes from several regions of the brain and spinal cord in adolescent and adult mice, which allowed them to see the diversity of these cells with unprecedented detail and clarity.

Unexpected Diversity of 12 Subclasses

Dr. Linnarsson, from the Institutet’s Department of Medical Biochemistry and Biophysics, said: “We uncovered an unexpected diversity within the oligodendrocyte population.

“In this study, we have identified 12 subclasses and a novel cell, distinct from oligodendrocytes, residing in the blood vessels.”

Researchers found that the initial stages of gaining maturity in oligodendrocyte development were similar across the central nervous system in juvenile mice, whereas different subsets of mature cells were enriched in specific regions in adult brains.

Dr. Gonçalo Castelo-Branco, of the same department, said that the uncovering of this unexpected diversity might bring new insights on mechanisms of degeneration and regeneration of diseases where myelin is lost, such as multiple sclerosis.

The research has been supported by, among others, the Swedish Research Council, Swedish Brain Foundation (Hjärnfonden), Swedish Society of Medicine (SLS), Åke Wiberg, Clas Groschinsky, Petrus och Augusta Hedlunds foundation, and European Union.

¹ “Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system,” Sueli Marques, Amit Zeisel, Simone Codeluppi, David van Bruggen, Ana Mendanha, Falcão, Lin Xiao, Huiliang Li, Martin Häring, Hannah Hochgerner, Roman A. Romanov, Daniel Gyllborg, Ana Muñoz Manchado, Gioele La Manno, Peter Lönnerberg, Elisa M. Floriddia, Fatemah Rezayee, Patrik Ernfors, Ernest Arenas, Jens Hjerling-Leffler, Tibor Harkany, William D. Richardson, Sten Linnarsson, Gonçalo Castelo-Branco. Science, DOI: 10.1126/science.aaf6463, published online June 10, 2016.