Project description:Identification of AP-2d target genes in the midbrain of E15 mouse embryos RNA from a pool of 15 E15 mouse midbrains from control and AP-2d knockout embryos
Project description:To explore the differentially expressed genes in embryonic midbrain development in Wnt1-lineage specific Gpr161 deleted mouse embryos.
Project description:This phase I trial is studying the best dose of 3-AP and the side effects of giving 3-AP together with gemcitabine in treating patients with advanced solid tumors or lymphoma. Drugs used in chemotherapy, such as 3-AP and gemcitabine (GEM), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help gemcitabine kill more cancer cells by making the cells more sensitive to the drug. 3-AP may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Project description:Astrocytes are increasingly recognised as essential contributors to both physiological brain function and neurodegenerative diseases. Here, we describe how the Parkinson’s disease (PD)-associated mutation LRRK2-G2019S affects astrocytes using autoptic brain samples and PD patient-specific 3D midbrain organoids and 2D astrocytes derived from induced pluripotent stem cells. In autoptic midbrain samples from LRRK2-G2019S patients, we observed a reduction in GFAP⁺ astrocytes but increased branching, together with transcriptional signatures consistent with altered astrocyte function. We also observed delayed astrocyte differentiation in PD patient-specific midbrain organoids, accompanied by altered astrocyte transcriptomic profiles revealed by single-cell RNA sequencing. This defective differentiation contributes to the acquisition of a senescent-like phenotype. In 2D cultures, astrocyte differentiation from LRRK2-G2019S precursor cells was associated with early apoptosis and altered Wnt/β-catenin and TGFβ signalling compared to LRRK2-WT cultures. Notably, pharmacological activation of the developmental transcription factor NR2F1, downregulated in LRRK2-G2019S models, reduced astrocyte cell death and senescence-like phenotypes. Together, these data show that LRRK2-G2019S impairs astrocyte specification and predisposes to a senescent phenotype.
Project description:The data revealed differential expression between floor plate and ventral lateral region in E10.5 mouse embryo midbrain. Several differentially expressed genes in these regions have been reported in the literature, demonstrating reliability of tissue dissection. Midbrain floor plate and non-overlapping adjacent ventral lateral region of mouse E10.5 embryo midbrain was dissected. Each sample was a pool from 6 embryos. Three replicates for each region were used for the experiment.
Project description:Transcription factor Gata2 has been shown to regulate the development of the GABAergic neurons in the mouse midbrain. To gain information about the possible target genes of the Gata2 transcription factor, we used cDNA microarrays to compare gene expression in the embryonic day 12.5 (E12.5) wild-type and Gata2 mutant embryos. In this dataset, gene expression in control and Gata2cko dorsal and ventral midbrain tissues is reported. The ventral_mb_mut_rep3 sample was identified as outlier in sample correlation analysis and excluded from the differential gene expression analysis. The samples 13-18 are part of the GEO dataset GSE89354:GSM2367121-GSM2367126.