Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2022.919462/full |
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| author | Chiara Galante Nicolás Marichal Franciele Franco Scarante Franciele Franco Scarante Litsa Maria Ghayad Youran Shi Youran Shi Carol Schuurmans Carol Schuurmans Carol Schuurmans Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Sophie Péron Sophie Péron |
| author_facet | Chiara Galante Nicolás Marichal Franciele Franco Scarante Franciele Franco Scarante Litsa Maria Ghayad Youran Shi Youran Shi Carol Schuurmans Carol Schuurmans Carol Schuurmans Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Sophie Péron Sophie Péron |
| author_sort | Chiara Galante |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-09T16:08:37Z |
| format | Article |
| id | doaj.art-668005160f64403abd45312db5c36dfd |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-09T16:08:37Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-668005160f64403abd45312db5c36dfd2023-04-24T15:15:25ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-12-011610.3389/fnins.2022.919462919462Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivoChiara Galante0Nicolás Marichal1Franciele Franco Scarante2Franciele Franco Scarante3Litsa Maria Ghayad4Youran Shi5Youran Shi6Carol Schuurmans7Carol Schuurmans8Carol Schuurmans9Benedikt Berninger10Benedikt Berninger11Benedikt Berninger12Benedikt Berninger13Benedikt Berninger14Sophie Péron15Sophie Péron16Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, GermanyCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomDepartment of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, BrazilCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomThe Francis Crick Institute, London, United KingdomBiological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, CanadaDepartment of Biochemistry, University of Toronto, Toronto, ON, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaInstitute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, GermanyCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomThe Francis Crick Institute, London, United KingdomMRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomFocus Program Translational Neuroscience, Johannes Gutenberg University, Mainz, GermanyInstitute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, GermanyCentre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United KingdomThe 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.https://www.frontiersin.org/articles/10.3389/fnins.2022.919462/fullastrocytegliogenesislineage reprogrammingneurogenesisproliferationproneural |
| spellingShingle | Chiara Galante Nicolás Marichal Franciele Franco Scarante Franciele Franco Scarante Litsa Maria Ghayad Youran Shi Youran Shi Carol Schuurmans Carol Schuurmans Carol Schuurmans Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Benedikt Berninger Sophie Péron Sophie Péron Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo Frontiers in Neuroscience astrocyte gliogenesis lineage reprogramming neurogenesis proliferation proneural |
| title | Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo |
| title_full | Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo |
| title_fullStr | Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo |
| title_full_unstemmed | Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo |
| title_short | Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo |
| title_sort | enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated achaete scute complex like 1 overexpression in the postnatal cerebral cortex in vivo |
| topic | astrocyte gliogenesis lineage reprogramming neurogenesis proliferation proneural |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2022.919462/full |
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