Single-cell transcriptomic profiling of progenitors of the oligodendrocyte lineage reveals transcriptional convergence during development

Marques, S.; Vanichkina, D.; van Bruggen, D.; Floriddia, E.; Munguba, H.; Varemo, L.; Giacomello, S.; Mendanha Falcao, A.; Meijer, M.; Samudyata, S.; Codeluppi, S.; Bjorklund, A.; Linnarsson, S.; Hjerling-Leffler, J.; Taft, R.; Castelo-Branco, G.

doi:10.1101/186445

bioRxiv · 10.1101/186445

Single-cell transcriptomic profiling of progenitors of the oligodendrocyte lineage reveals transcriptional convergence during development

Marques, S.·Vanichkina, D.·van Bruggen, D.·Floriddia, E.·Munguba, H.·Varemo, L.·Giacomello, S.·Mendanha Falcao, A.·Meijer, M.·Samudyata, S.·Codeluppi, S.·Bjorklund, A.·Linnarsson, S.·Hjerling-Leffler, J.·Taft, R.·Castelo-Branco, G.

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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 transcriptional oligodendrocyte (OL) states at adult stages. Here we present a bulk and single-cell transcriptomics resource providing insights on how transitions between these states occur. We show that E13.5 Pdgfra+ populations are not OPCs, exhibiting instead hallmarks of neural progenitors. A subset of these progenitors, which we refer as pre-OPCs, rewires their transcriptional landscape, converging into indistinguishable OPC states at E17.5 and post-natal stages. P7 brain and spinal cord OPCs present similar transcriptional profiles at the single-cell level, indicating that OPC states are not region-specific. Postnatal OPC progeny of E13.5 Pdgfra+ have electrophysiological and transcriptional profiles similar to OPCs derived from subsequent specification waves. In addition, lineage tracing indicates that a subset of E13.5 Pdgfra+ cells also originate cells of the pericyte lineage. In summary, our results indicate that embryonic Pdgfra+ cells are diverse and give rise at post-natal stages to distinct cell lineages, including OPCs with convergent transcriptional profiles in different CNS regions.

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Marques, S., Vanichkina, D., van Bruggen, D., Floriddia, E., Munguba, H., Varemo, L., Giacomello, S., Mendanha Falcao, A., Meijer, M., Samudyata, S., Codeluppi, S., Bjorklund, A., Linnarsson, S., Hjerling-Leffler, J., Taft, R., Castelo-Branco, G.. 2017-09-17. Single-cell transcriptomic profiling of progenitors of the oligodendrocyte lineage reveals transcriptional convergence during development. https://doi.org/10.1101/186445

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