Enhanced proliferation of oligodendrocyte progenitor cells following retrovirus mediated Achaete-scute complex-like 1 overexpression in the postnatal cerebral cortex in vivo

• Published in: Frontiers in neuroscience 2022-12, Vol.16, p.919462-919462
• Main Authors: Galante, Chiara, Marichal, Nicolás, Scarante, Franciele Franco, Ghayad, Litsa Maria, Shi, Youran, Schuurmans, Carol, Berninger, Benedikt, Péron, Sophie
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; ASCL1 protein; astrocyte; Astrocytes; Cell cycle; Cell fate; Cell proliferation; Cerebral cortex; Doublecortin protein; Epidermal growth factor; Fate maps; Gene mapping; Genes; Glial cells; Glial fibrillary acidic protein; Glial stem cells; gliogenesis; lineage reprogramming; Neural stem cells; Neurogenesis; Neuronal-glial interactions; Neurons; Neuroscience; Progenitor cells; proliferation; proneural; Proteins; Sox10 protein
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2022.919462

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. , 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 . 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 , 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.