Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Cancer Research Institute of Jilin University, The First Hospital of Jilin University, Changchun, Jilin, China
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Cancer Biology Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, United States
Chenxi He
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
Qiang Zhang
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States
Department of Neuroscience, Baylor College of Medicine, Houston, United States
Jiangong Ren
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States
Congxin Dai
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China
Rocío I Zorrilla-Veloz
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Cancer Biology Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, United States
Takashi Shingu
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States
Liang Yuan
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Graduate School of Biomedical Sciences, Tufts University, Boston, United States
Yunfei Wang
Clinical Science Division, H. Lee Moffitt Cancer Center & Research Institute, Tampa, United States
Yiwen Chen
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, United States
Fei Lan
Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, United States; Cancer Biology Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, United States; Neuroscience Program, MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, United States
Myelination depends on timely, precise control of oligodendrocyte differentiation and myelinogenesis. Cholesterol is the most abundant component of myelin and essential for myelin membrane assembly in the central nervous system. However, the underlying mechanisms of precise control of cholesterol biosynthesis in oligodendrocytes remain elusive. In the present study, we found that Qki depletion in neural stem cells or oligodendrocyte precursor cells in neonatal mice resulted in impaired cholesterol biosynthesis and defective myelinogenesis without compromising their differentiation into Aspa+Gstpi+ myelinating oligodendrocytes. Mechanistically, Qki-5 functions as a co-activator of Srebp2 to control transcription of the genes involved in cholesterol biosynthesis in oligodendrocytes. Consequently, Qki depletion led to substantially reduced concentration of cholesterol in mouse brain, impairing proper myelin assembly. Our study demonstrated that Qki-Srebp2-controlled cholesterol biosynthesis is indispensable for myelinogenesis and highlights a novel function of Qki as a transcriptional co-activator beyond its canonical function as an RNA-binding protein.
