New brain mapping method reveals new cell types

A new, detailed map of the cerebral cortex, created by researchers at the Karolinska Institutet, has revealed previously unknown cell types and the genes active within them.

Historically, maps of the brain have identified cells through characteristics like location, morphology and properties. These cell attributes alone do not contain enough information to identify cell type in all circumstances.

The study, led by Dr Jens Hjerling-Leffler and Dr Sten Linnarsson, used single-cell RNA sequencing (scRNA-seq) to analyse the transcriptome of 3005 cells within the cortex.

This is the first time this method has been used to identify cells at this scale on such complex tissue.

The transcriptome is the group of all RNA molecules within a cell or specific population of cells. It normally includes the quantities, as well as the identities of the set of molecules.

Single-cell RNA sequencing is a way of identifying the transcriptome of a cell, including the relative abundance of each RNA molecule. This data can then be used to create a profile of the genes that are expressed within that cell and therefore identify the cell type.

By comparing which of the approximately 20,000 genes were active in each cell, they sorted them into nine major classes and 47 molecularly distinct subclasses.

Using the new map, the researchers identified several new cell types. This included an interneuron subclass and six subpopulations of oligodendrocyte. Oligodendrocytes are responsible for forming the myelin sheath that insulates nerve cells. This knowledge may help us better understand myelin related diseases, like multiple sclerosis (MS).

Jens Hjerling-Leffler said:

"Above all, we have created a much more detailed map of the cells of the brain that describes each cell type in detail and shows which genes are active in it. This gives science a new tool for studying these cell types in disease models and helps us to understand better how brain cells respond to disease and injury."

Research Paper

Zeisel. A, Muñoz-Manchado A. B., Codeluppi S., Lönnerberg P., La Manno G., Juréus A., Sueli Marques J., Munguba H., Liqun L., Betsholtz C., Rolny C., Castelo-Branco G., Jens Hjerling-Leffler., Linnarsson S. (2015) Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq Science 347;6226 1138-1142 doi: 10.1126/science.aaa1934