Project description:This study is to analyze the transcriptomic profiles of Plp-CreERT2;QKLoxP/LoxP (Qk-KO) and Plp-CreERT2;QKLoxP/+ (WT) mice and WT and Qk-KO oligodendrocytes to determine the differentially expressed genes.
Project description:Lipid-rich myelin forms insulating axon-wrapping multilayers essential for neural function, but how mature myelin maintains its structural lipid components remains obscure. Here we identify Quaking (Qki) as a major regulator of myelin lipid homeostasis. Qki depletion in adult myelinating oligodendrocytes disrupted myelin lipid metabolism and caused demyelination, resulting in progressive neurological deficits that could be partially rescued by high-fat diet. Mechanistically, Qki serves as a coactivator of the PPARb-RXRa complex, which controls transcription of lipid-metabolism genes, particularly those for fatty acid desaturation and elongation. Treatment of Qki-depleted mice with PPARb or RXR agonists alleviated neurological disability and significantly extended mouse survival. Furthermore, a subset of lesions from patients with primary progressive multiple sclerosis were characterized by preferential reduction of myelin lipids and activities of lipid-metabolism pathways. Together, our findings demonstrate that continuous lipid synthesis is indispensable for mature myelin maintenance and highlight an underappreciated role of lipid metabolism in demyelinating diseases.
Project description:This study is to analyze the transcriptomic profiles of 6 weeks 0.2% cuprizone treated Cx3cr1-CreER;QKLoxP/LoxP (Qk-KO) and Cx3cr1-CreER;QK LoxP/+ (WT) mice
Project description:During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.
Project description:During mammalian brain development, neural stem cells (NSCs) initially produce only neurons and subsequently shift to glial production, while it is still unknown what regulates this drastic fate change. Here we discovered RNA-binding protein (RBP) of quaking (Qk) is selectively expressed in NSCs and is essential for switching from neurogenesis to gliogenesis. Using CNS-specific KO mice for Qk, we found that gliogenesis, but not neurogenesis, was specifically disrupted in Qk-/- brains. In glial differentiating condition, Qk-/- NSCs failed to enter gliogenesis but caused ectopic neurogenic gene expression. Pathway analysis of Qk-/- NSCs identified endocytosis as the regulatory functional cluster of Qk which has been shown to facilitate extra-cellular signaling receptors replacement and promote NSC differentiation. Mechanistically, Qk regulates endocytosis pathway genes through stabilizing their mRNAs via Qk binding sequences in 3’UTR. These results uncovered the cell fate determination mechanism of NSCs through mRNA regulation.
Project description:We showed that the composition of the nuclear lamina changes with the differentiation state of oligodendrocyte lineage cells, with Lamin B highly expressed in progenitor cells and Lamin A highly expressed in mature oligodendrocytes. The genetic deletion of LMNA in mice results in the onset of a progressive motor phenotype in adult mice. We performed ATAC-Seq in myelinating Oligodendrocytes expressing the myelin marker NDRG1-EGFP ( Marechal et al., 2021) in the presence or absence of LMNA. The goal is to identify regions of chromatin accessibility that distinguish the LMNA KO mutant cells from the WT.
Project description:In order to study the importance of HSFA1 in thermotolerance in Arabidopsis, we generated the HSFA1a, b, d and e quadruple mutant (QK). QK is very sensitive to heat. Therefore, we used microarray to study how many genes regulated by HSFA1 after heat shock. Seven-day-old seedlings of Col-0, Ws and QK grown at 22oC on 0.5x MS plates containing 1% sucrose were incubated for 1 h at 37 °C. Subsequently, samples were collected for RNA extraction. The experiment was repeated, and two biological replicates were processed for analysis.
Project description:This study is to analyze the transcriptomic profiles of Rosa26-CreERT2;QkLoxP/LoxP (Qk-Rosa26-iCKO) mice and littermate controls to determine the differentially expressed genes after Qk deletion.