Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development

Sueli Marques; David van Bruggen; Darya Pavlovna Vanichkina; Elisa Mariagrazia Floriddia; Hermany Munguba; Leif Väremo; Stefania Giacomello; Ana Mendanha Falcão; Mandy Meijer; Åsa Kristina Björklund; Jens Hjerling-Leffler; Ryan James Taft; Gonçalo Castelo-Branco

doi:10.1016/j.devcel.2018.07.005

Transcriptional Convergence of Oligodendrocyte Lineage Progenitors during Development

Dev Cell. 2018 Aug 20;46(4):504-517.e7. doi: 10.1016/j.devcel.2018.07.005. Epub 2018 Aug 2.

Affiliations

¹ Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden.
² Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, Camperdown, NSW 2050, Australia; Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4067, Australia.
³ Science for Life Laboratory, Department of Biology and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Göteborg 412 96, Sweden.
⁴ Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Box 1031, 17121 Solna, Sweden.
⁵ Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Husargatan 3, 75237 Uppsala, Sweden.
⁶ Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4067, Australia; Illumina, Inc., San Diego, CA 92122, USA.
⁷ Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Biomedicum, Karolinska Institutet, Stockholm 17177, Sweden. Electronic address: goncalo.castelo-branco@ki.se.

Abstract

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.

Keywords: myelin; neural development; neural progenitors; oligodendrocyte; oligodendrocyte precursor cell; pericyte; platelet-derived growth factor receptor alpha; single-cell RNA-seq; transcription factors; transcriptomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation / physiology*
Cell Lineage / physiology*
Cell Proliferation / physiology*
Cells, Cultured
Oligodendroglia / cytology*
Receptor, Platelet-Derived Growth Factor alpha / metabolism
Spinal Cord / metabolism
Stem Cells / cytology

Substances

Receptor, Platelet-Derived Growth Factor alpha