Early cortical oligodendrocyte precursor cells are transcriptionally distinct and lack synaptic connections.

Autor: Vana NS; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.; Department of Neuropathology, University Hospital Bonn, Bonn, Germany., van Loo KMJ; Department of Neuropathology, University Hospital Bonn, Bonn, Germany., van Waardenberg AJ; i-Synapse, Bioinformatics, Cairns, Australia., Tießen M; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany., Cases-Cunillera S; Department of Neuropathology, University Hospital Bonn, Bonn, Germany., Sun W; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany., Quatraccioni A; Department of Neuropathology, University Hospital Bonn, Bonn, Germany., Schoch S; Department of Neuropathology, University Hospital Bonn, Bonn, Germany., Dietrich D; Department of Neurosurgery, University Hospital Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: Glia [Glia] 2023 Sep; Vol. 71 (9), pp. 2210-2233. Date of Electronic Publication: 2023 May 25.
DOI: 10.1002/glia.24388
Abstrakt: Oligodendrocyte precursor cells (OPCs) generate oligodendrocytes, a process that may be tuned by neuronal activity, possibly via synaptic connections to OPCs. However, a developmental role of synaptic signaling to OPCs has so far not been shown unequivocally. To address this question, we comparatively analyzed functional and molecular characteristics of highly proliferative and migratory OPCs in the embryonic brain. Embryonic OPCs in mice (E18.5) shared the expression of voltage-gated ion channels and their dendritic morphology with postnatal OPCs, but almost completely lacked functional synaptic currents. Transcriptomic profiling of PDGFRα +  OPCs revealed a limited abundance of genes coding for postsynaptic signaling and synaptogenic cell adhesion molecules in the embryonic versus the postnatal period. RNA sequencing of single OPCs showed that embryonic synapse-lacking OPCs are found in clusters distinct from postnatal OPCs and with similarities to early progenitors. Furthermore, single-cell transcriptomics demonstrated that synaptic genes are transiently expressed only by postnatal OPCs until they start to differentiate. Taken together, our results indicate that embryonic OPCs represent a unique developmental stage biologically resembling postnatal OPCs but without synaptic input and a transcriptional signature in the continuum between OPCs and neural precursors.
(© 2023 The Authors. GLIA published by Wiley Periodicals LLC.)
Databáze: MEDLINE