Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors
Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors
ABSTRACT Capicua (Cic) is a transcriptional repressor mutated in the brain cancer oligodendroglioma. Despite its cancer link, little is known of Cic’s function in the brain. Here, we investigated the relationship between Cic expression and cell type specification in the brain. Cic is strongly expressed in astrocytic and neuronal lineage cells but is more weakly expressed in stem cells and oligodendroglial lineage cells. Using a new conditional Cic knockout mouse, we show that forebrain-specific Cic deletion increases proliferation and self-renewal of neural stem cells. Furthermore, Cic loss biases neural stem cells toward glial lineage selection, expanding the pool of oligodendrocyte precursor cells (OPCs). These proliferation and lineage selection effects in the developing brain are dependent on de-repression of Ets transcription factors. In patient-derived oligodendroglioma cells, CIC re-expression or ETV5 blockade decreases lineage bias, proliferation, self-renewal and tumorigenicity. Our results identify Cic is an important regulator of cell fate in neurodevelopment and oligodendroglioma, and suggest that its loss contributes to oligodendroglioma by promoting proliferation and an OPC-like identity via Ets overactivity.
Chen Myra J.、Adnani Lata、Blough Michael D.、Robbins Stephen M.、Rogers Alexandra D.、Frankiw Luke S.、Lawn Samuel O.、Wu Wei、Alshehri Mana、Dixit Rajiv、Cairncross J. Gregory、Ahmad Shiekh Tanveer、Schuurmans Carol、Chan Jennifer A.
Charbonneau Cancer Institute, University of Calgary||Alberta Children?ˉs Hospital Research Institute, University of CalgaryAlberta Children?ˉs Hospital Research Institute, University of Calgary||Sunnybrook Research Institute and the Department of Biochemistry, University of TorontoCharbonneau Cancer Institute, University of CalgaryCharbonneau Cancer Institute, University of CalgaryCharbonneau Cancer Institute, University of CalgaryCharbonneau Cancer Institute, University of Calgary||Department of Biology & Bioengineering, California Institute of TechnologyCharbonneau Cancer Institute, University of Calgary||ZymeworksCharbonneau Cancer Institute, University of Calgary||University of CaliforniaCharbonneau Cancer Institute, University of Calgary||King Abdullah International Medical CentreCharbonneau Cancer Institute, University of Calgary||Alberta Children?ˉs Hospital Research Institute, University of Calgary||Sunnybrook Research Institute and the Department of Biochemistry, University of TorontoCharbonneau Cancer Institute, University of CalgaryDepartment of Pathology & Laboratory Medicine, University of Calgary||Charbonneau Cancer Institute, University of Calgary||Alberta Children?ˉs Hospital Research Institute, University of CalgaryAlberta Children?ˉs Hospital Research Institute, University of Calgary||Sunnybrook Research Institute and the Department of Biochemistry, University of TorontoDepartment of Pathology & Laboratory Medicine, University of Calgary||Charbonneau Cancer Institute, University of Calgary||Alberta Children?ˉs Hospital Research Institute, University of Calgary
神经病学、精神病学基础医学肿瘤学
CapicuaCIColigodendrogliomagliomaoligodendrocyte precursor cellcell fate specificationgliogenesisEtv5
Chen Myra J.,Adnani Lata,Blough Michael D.,Robbins Stephen M.,Rogers Alexandra D.,Frankiw Luke S.,Lawn Samuel O.,Wu Wei,Alshehri Mana,Dixit Rajiv,Cairncross J. Gregory,Ahmad Shiekh Tanveer,Schuurmans Carol,Chan Jennifer A..Capicua regulates neural stem cell proliferation and lineage specification through control of Ets factors[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/335984.点此复制
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