2018 Seminar series "Transcriptional and epigenetic states of oligodendrocyte lineage cells in the central nervous system: insights form single cell omics"
Dr Gonçalo Castelo-Branco
Associate Professor, Department of Medical Biochemistry and Biophysics and Ming Wai Lau Centre for Reparative Medicine, Stockholm node, Karolinska Institutet
Date: 29th October 2018 (Monday)
Time: 2:00 pm – 3:00 pm
Venue: Ming Wai Lau Centre for Reparative Medicine, Science Park, Sha Tin
Abstract
Oligodendrocytes 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 fails in progressive MS. In order to clearly define transcriptional states of OPCs and other oligodendrocyte lineage cells during development and disease, we have performed single-cell RNA-Seq of cells of the oligodendrocyte lineage from healthy mouse CNS and also from a mouse model of MS. We identified several cell states/populations, representing unique stages during the process of differentiation, myelination and final stages of maturation. Our results also indicate that diverse embryonic progenitor cells of the oligodendrocyte 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 oligodendrocytes occurs in the juvenile/adult CNS, as the neuronal circuitry matures. We also identified unique OLs and OPCs in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, expressing genes involved in antigen processing and presentation and immunoprotection. Thus, our results indicate a previously unanticipated heterogeneity of the oligodendrocyte lineage during development and disease.
Biography
Dr Gonçalo Castelo-Branco is an Associate Professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Sweden. His research group is interested in the molecular mechanisms defining the transcriptomic and epigenomic states of oligodendrocyte lineage cells in development and disease, at a population and single-cell level. His group is particularly focused on how interplay between transcription factors, non-coding RNAs and chromatin modifying enzymes contributes to the transition between epigenetic states in oligodendrocytes, with the aim to design epigenetic based-therapies to induce regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis.