TY - JOUR
T1 - Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
AU - Galante, Chiara
AU - Marichal, Nicolas
AU - Franco Scarante, Franciele
AU - Ghayad, Litsa Maria
AU - Shi, Youran
AU - Schuurmans, Carol
AU - Berninger, Benedikt
AU - Peron, Sophie
N1 - Funding Information:
This research was funded in part by the Wellcome Trust (206410/Z/17/Z). For the purpose of open access, the author has applied a CC BY public copyright license to any author accepted manuscript version arising from this submission. This study was also supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement No. 101021560, IMAGINE), the German Research Foundation (BE 4182/11-1 project number 357058359; CRC1080, project No. 221828878), and the research initiative of Rheinland-Pfalz at the Johannes Gutenberg University Mainz (ReALity) to BB, by the Inneruniversitäre Forschungsförderung Stufe I of the Johannes Gutenberg University Mainz to SP, and by core funding to the Francis Crick Institute from Cancer Research United Kingdom, The Medical Research Council, and the Wellcome Trust (FC001002). NM was supported by a fellowship from the Human Frontiers Science Program (HFSP Long-Term Fellowship, LT000646/2015). FS was supported by a fellowship from São Paulo Research Foundation (FAPESP) process No. 2021/13515-5.
Funding Information:
We are grateful to the members of the Berninger laboratory for their helpful comments and critical feedback over the course of this study. We are grateful to B. Rico (King’s College London) for her support throughout the project. We acknowledge support from the Microscopy Core Facility of the Institute of Molecular Biology (IMB) Mainz. The data published in this work are partially included in the doctoral thesis of CG published by the Johannes Gutenberg-Universität Mainz () and in a preprint server (; doi: 10.1101/2022.04.13.488173 ).
Publisher Copyright:
Copyright © 2022 Galante, Marichal, Scarante, Ghayad, Shi, Schuurmans, Berninger and Péron.
PY - 2022/12/2
Y1 - 2022/12/2
N2 - The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In vitro, Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells. Here, we examined whether Ascl1 can similarly induce neuronal reprogramming of glia undergoing proliferation in the postnatal mouse cerebral cortex in vivo. Toward this goal, we targeted cortical glia during the peak of proliferative expansion (i.e., postnatal day 5) by injecting a retrovirus encoding for Ascl1 into the mouse cerebral cortex. In contrast to the efficient reprogramming observed in vitro, in vivo Ascl1-transduced glial cells were converted into doublecortin-immunoreactive neurons only with very low efficiency. However, we noted a drastic shift in the relative number of retrovirus-transduced Sox10-positive oligodendrocyte progenitor cells (OPCs) as compared to glial fibrillary acidic protein (GFAP)-positive astrocytes. Genetic fate mapping demonstrated that this increase in OPCs was not due to Ascl1-mediated astrocyte-to-OPC fate conversion. Rather, EdU incorporation experiments revealed that Ascl1 caused a selective increase in proliferative activity of OPCs, but not astrocytes. Our data indicate that rather than inducing neuronal reprogramming of glia in the early postnatal cortex, Ascl1 is a selective enhancer of OPC proliferation.
AB - The proneural transcription factor Achaete-scute complex-like 1 (Ascl1) is a major regulator of neural fate decisions, implicated both in neurogenesis and oligodendrogliogenesis. Focusing on its neurogenic activity, Ascl1 has been widely used to reprogram non-neuronal cells into induced neurons. In vitro, Ascl1 induces efficient reprogramming of proliferative astroglia from the early postnatal cerebral cortex into interneuron-like cells. Here, we examined whether Ascl1 can similarly induce neuronal reprogramming of glia undergoing proliferation in the postnatal mouse cerebral cortex in vivo. Toward this goal, we targeted cortical glia during the peak of proliferative expansion (i.e., postnatal day 5) by injecting a retrovirus encoding for Ascl1 into the mouse cerebral cortex. In contrast to the efficient reprogramming observed in vitro, in vivo Ascl1-transduced glial cells were converted into doublecortin-immunoreactive neurons only with very low efficiency. However, we noted a drastic shift in the relative number of retrovirus-transduced Sox10-positive oligodendrocyte progenitor cells (OPCs) as compared to glial fibrillary acidic protein (GFAP)-positive astrocytes. Genetic fate mapping demonstrated that this increase in OPCs was not due to Ascl1-mediated astrocyte-to-OPC fate conversion. Rather, EdU incorporation experiments revealed that Ascl1 caused a selective increase in proliferative activity of OPCs, but not astrocytes. Our data indicate that rather than inducing neuronal reprogramming of glia in the early postnatal cortex, Ascl1 is a selective enhancer of OPC proliferation.
UR - http://www.scopus.com/inward/record.url?scp=85144135535&partnerID=8YFLogxK
U2 - 10.3389/fnins.2022.919462
DO - 10.3389/fnins.2022.919462
M3 - Article
SN - 1662-453X
VL - 16
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 919462
ER -