Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development

• Published in: Developmental cell Vol. 46; no. 4; pp. 504 - 517.e7
• Main Authors: Marques, Sueli, van Bruggen, David, Vanichkina, Darya Pavlovna, Floriddia, Elisa Mariagrazia, Munguba, Hermany, Väremo, Leif, Giacomello, Stefania, Falcão, Ana Mendanha, Meijer, Mandy, Björklund, Åsa Kristina, Hjerling-Leffler, Jens, Taft, Ryan James, Castelo-Branco, Gonçalo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.08.2018; Cell Press
• Subjects: Animals; Cell Differentiation - physiology; Cell Lineage - physiology; Cell Proliferation - physiology; Cells, Cultured; myelin; neural development; neural progenitors; oligodendrocyte; oligodendrocyte precursor cell; Oligodendroglia - cytology; pericyte; platelet-derived growth factor receptor alpha; Receptor, Platelet-Derived Growth Factor alpha - metabolism; single-cell RNA-seq; Spinal Cord - metabolism; Stem Cells - cytology; transcription factors; transcriptomics; myelin; oligodendrocyte precursor cell; pericyte; transcription factors; platelet-derived growth factor receptor alpha; oligodendrocyte; transcriptomics; neural progenitors; single-cell RNA-seq; neural development
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2018.07.005

Pdgfra+ oligodendrocyte precursor cells (OPCs) arise in distinct specification waves during embryogenesis in the central nervous system (CNS). It is unclear whether there is a correlation between these waves and different oligodendrocyte (OL) states at adult stages. Here, we present bulk and single-cell transcriptomics resources providing insights on how transitions between these states occur. We found that post-natal OPCs from brain and spinal cord present similar transcriptional signatures. Moreover, post-natal OPC progeny of E13.5 Pdgfra+ cells present electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves, indicating that Pdgfra+ pre-OPCs rewire their transcriptional network during development. Single-cell RNA-seq and lineage tracing indicates that a subset of E13.5 Pdgfra+ cells originates cells of the pericyte lineage. Thus, our results indicate that embryonic Pdgfra+ cells in the CNS give rise to distinct post-natal cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions. [Display omitted] •OPCs arising from different parts of the CNS are highly similar to one another•Pre-OPCs converge into similar transcriptional and electrophysiological OPC states•E13.5 Pdgfra+ cells give rise mainly to OPCs in the post-natal CNS•E13.5 Pdgfra+ cells also give rise to cells of the pericyte lineage Marques, van Bruggen, Vanichkina et al. present a bulk and single-cell transcriptomics resource of mouse forebrain and spinal cord Pdgfra+ cells at embryonic and post-natal stages. Embryonic Pdgfra+ cells produce distinct post-natal cell lineages. Post-natal oligodendrocyte precursor cells arising from different CNS regions are ultimately highly similar.