Description

Transcriptional states of oligodendrocyte lineage cells in the central nervous system: converge and divergence during development and in disease

Gonçalo Castelo-Branco^1*

¹Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden

*Corresponding Author

Oligodendrocytes (OL) are glial cells that mediate myelination of neurons, a process that allows efficient electrical impulse transmission in the central nervous system (CNS). An autoimmune response against myelin triggers demyelination in multiple sclerosis (MS). Oligodendrocyte precursor cells (OPCs) can initially differentiate and promote remyelination in MS, but this process eventually becomes defective in progressive MS. We have performed single-cell and bulk RNA sequencing of cells of the OL lineage from mouse CNS, during development and in a mouse model of multiple sclerosis. We identified several novel cell states/populations within the OL lineage after birth, representing unique stages during the process of differentiation, myelination and final stages of maturation (1). Our results also indicate that diverse embryonic progenitor cells of the OL lineage from different regions of the CNS converge into cell states compatible with differentiation at postnatal stages, while subsequent divergence of the mature terminal differentiated OLs occurs in the juvenile/adult CNS, as the neuronal circuitry matures. We also identify distinct OL cell states present in a mouse model of multiple sclerosis. Thus, our results indicate a previously unanticipated heterogeneity of the OL lineage in development and in disease.

Reference: (1) Marques, Zeisel et al., Science 2016

Funding Acknowledgements: Swedish Research Council, European Union (European Research Council, Horizon 2020, Marie Curie, FP7), Ming Wai Lau Centre for Reparative Medicine, Cancerfonden, Swedish Brain Foundation, Petrus och Augusta Hedlunds, Cancerfonden, Karolinska Institutet.