Distinct cell states within the oligodendrocyte lineage in the mouse brain: insights from single-cell RNA-Seq
David van Bruggen1, Sueli Marques1, Samudyata1, Amit Zeisel1, Gonçalo Castelo-Branco1
1Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Oligodendrocytes (OLs), originating from the glial lineage are myelinating cells populating the CNS that facilitate electrical impulse transmission through axon ensheathment. In demyelinating diseases neurodegeneration occurs, particularly in multiple sclerosis (MS) where an immune response is mounted against myelin. Oligodendrocyte precursor cells (OPCs ) are recruited to lesions and remyelinate axons, however, this mechanism fails in progressive MS. The oligodendrocyte lineage, from OPCs towards mature OLs, involves transitions along several states that define differentiation and myelination potential. To reveal distinct epigenetic states during development, we have individually sequenced 6565 cells belonging to the oligodendrocyte lineage from the mouse brain with developmental time points ranging from embryonic day 13.5 to postnatal day 90. We identified several well-defined populations of oligodendrocyte lineage cells reflecting unique stages during the process of differentiation and myelination. Embryonic day 13.5 obtained cells clustered in multiple populations of progenitor cells related to OPCs, the latter of which our data suggests a universal differentiation path during early oligodendrocyte lineage differentiation and subsequent diversification in the mature OLs. To investigate the OL lineage, we developed a single-cell near-neighbor network embedding method (SCN3E), allowing us to cluster and order the cells according to each cells molecular profile and concurrently generate a pseudotime ordering. We resolve many regulators that show differential expression along the pseudotime axis, additionally, we identify non-coding RNAs uniquely expressed in these distinct populations, possibly contributing to transitions between the identified cell states.
Support: Swedish Research Council, European Union (Marie Curie, FP7), Swedish Brain Foundation, Swedish Society of Medicine, Clas Groschinsky foundation, Åke Wiberg Foundation, Hedlund Foundation, Karolinska Institutet Research Foundations.
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