Project description:Endothelial-derived Wnt/Ctnnb1-signaling is an important angiocrine regulator. Ctnnb1 gain-of-function (GOF) in sinusoidal endothelial cells was generated via Stab2-iCreF3tg/wt Ctnnb1(Ex3)fl/wt mice to analyze the effects of endothelial β-catenin signaling on bone marrow function. We used microarrays to detail the global programme of gene expression in bone marrow EMCN+ cells with β-catenin (Ctnnb1) gain-of-function compared to Wildtype.
Project description:Stab2-iCreF3tg/wt Ctnnb1(Ex3)fl/wt become anemic by the age of three months. We utilzed this model to investigated effects of niche Wnt-Signaling alterations on the terminal erythroid progenitor populations PIII (polychromatic erythroblasts) and PIV (orthochromatic erythroblasts and reticulocytes) by microarray transcriptome analysis.
Project description:Endothelial-derived Wnt/Ctnnb1-signaling is an important angiocrine regulator. Ctnnb1 gain-of-function (GOF) in liver sinusoidal endothelial cells was generated by crossing Clec4g-iCre (Wohlfeil SA et al, 2019, Cancer Research) with Ctnnb1(Ex3) fl/fl mice (Harada N et al, 1999, EMBO J) to analyze the effects of endothelial β-catenin signaling on LSEC differentiation and liver function We used microarrays to detail the global programme of gene expression in liver sinusoidal endothelial cells with β-catenin (Ctnnb1) gain-of-function compared to control animals.
Project description:To investigate the role of RNA methyltransferase METTL3-mediated m6A modification in macrophage, we performed m6A-sequencing to map the m6A modification in bone-marrow-derived macrophages (BMDMs) from Mettl3fl/fl (WT) and Mettl3fl/fl,LyzM-cre (cKO) mice
Project description:To investigate the role of RNA methyltransferase METTL3-mediated m6A modification in macrophage after co-culturing with MC38 cells, we performed m6A-sequencing to map the m6A modification in bone-marrow-derived macrophages (BMDMs) from Mettl3fl/fl (WT) and Mettl3fl/fl,LyzM-cre (cKO) mice
Project description:To comprehensively learn about the mechanisms of METTL3-mediated pro-tumoral functions, we performed RNA-sequencing to identify differentially expressed genes in bone-marrow-derived macrophages (BMDMs) in Mettl3fl/fl (WT) and LysM-cre, Mettl3fl/fl (KO) mice after co-cultured with MC38 cell line.
Project description:The goals of this study are to analyze NGS-derived spinal cord transcriptome profiling (RNA-seq) of wild type (WT), Nestin-Cre mediated Ctnnb1 Ex3 deletion (gain of function, dE3) and Ex2-6 deletion (loss of function, cKO) at embryonic day 13.5 (E13.5). Spinal cord RNA profiles were generated by deep sequencing, using Illumina Hiseq. The sequence reads that passed quality filters were analyzed at the transcript isoform level with HISAT2 and RSeQC.
Project description:Almost all medulloblastomas (MB) of the Wingless/Int-1 (WNT) type are characterized by hotspot mutations in CTNNB1, and mouse models have convincingly demonstrated the tumor-initiating role of these mutations. Additional alterations in SMARCA4 are detected in around 20% of WNT MB, but their functional role is mostly unknown. We therefore amended previously described Blbp cre::Ctnnb1(ex3)fl/wt mice by the introduction of a floxed Smarca4 allele. Unexpectedly, mutated β-catenin on its own induced severe developmental phenotypes in Blbp cre::Ctnnb1(ex3)fl/wt mice in our hands, including a thinned cerebral cortex, hydrocephalus, missing cerebellar layering, and non-proliferative cell accumulations in the brain stem and cerebellum. An additional loss of SMARCA4 even resulted in prenatal death for most mice. Respective Blbp cre::Ctnnb1(ex3)fl/wt::Smarca4fl/fl mutants developed large proliferative lesions in the cerebellum evolving from E13.5 to E16.5. Histological and molecular analysis of these lesions by DNA methylation profiling and single-cell RNA sequencing suggested an origin in early undifferentiated SOX2-positive cerebellar progenitors. Furthermore, upregulated WNT signaling, altered actin/cytoskeleton organization, and reduced neuronal differentiation were evident in mutant cells. In vitro, cells harboring alterations in both Ctnnb1 and Smarca4 were negatively selected and did not show tumorigenic potential after transplantation in adult recipient mice. However, in cerebellar explant cultures, mutant cells displayed significantly increased proliferation, suggesting an important role of the embryonic microenvironment in the development of lesions. Altogether, these results represent an important first step towards the unravelling of tumorigenic mechanisms induced by aberrant WNT signaling and SMARCA4 deficiency.
Project description:mRNAseq and proteomic data set of one week old WT (Chop wt/wt CkmmCre wt/wt Dars2 fl/fl), Chop KO (Chop ko/ko CkmmCre wt/wt Dars2 fl/fl), Dars2 KO (Chop wt/wt CkmmCre tg/wt Dars2 fl/fl) and DKO (Chop ko/ko CkmmCre tg/wt Dars2 fl/fl) mice