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

Neuroscience

Carol Schuurmans¹  Litsa Maria Ghayad²  Nicolás Marichal²  Franciele Franco Scarante³  Youran Shi⁴  Chiara Galante⁵  Sophie Péron⁶  Benedikt Berninger⁷ 

[1] Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON, Canada;Department of Biochemistry, University of Toronto, Toronto, ON, Canada;Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada;Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil;Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;The Francis Crick Institute, London, United Kingdom;Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, Germany;Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, Germany;Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;Institute of Physiological Chemistry, University Medical Center Johannes Gutenberg University, Mainz, Germany;Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;The Francis Crick Institute, London, United Kingdom;MRC Centre for Neurodevelopmental Disorders, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom;Focus Program Translational Neuroscience, Johannes Gutenberg University, Mainz, Germany;

关键词: astrocyte;    gliogenesis;    lineage reprogramming;    neurogenesis;    proliferation;    proneural;    Sox10;    Ascl1;   

DOI  :  10.3389/fnins.2022.919462

 received in 2022-04-13, accepted in 2022-11-09,  发布年份 2022

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2022 Galante, Marichal, Scarante, Ghayad, Shi, Schuurmans, Berninger and Péron.