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Basic Science and Pathogenesis.
Alzheimers Dement
December 2024
University of British Columbia, Vancouver, BC, Canada.
Background: Murine models of Alzheimer's Disease (AD) have resulted in numerous discoveries leading to a better understanding of AD pathogenesis but results poorly translated to novel treatment options. Over the past years, iPSC-derived human neuronal cultures have been developed to better model AD in vitro. One key hallmark of AD is the presence of insoluble Aß plaques in the brain.
View Article and Find Full Text PDFProbing Cell-Type Specificity of Mutant Phenotype at Transcriptomic Level Using Mosaic Analysis with Double Markers (MADM).
Methods Mol Biol
January 2025
Institute of Science and Technology Austria (ISTA), Klosterneuburg, Austria.
Mosaic Analysis with Double Markers (MADM) represents a mouse genetic approach coupling differential fluorescent labeling to genetic manipulations in dividing cells and their lineages. MADM uniquely enables the generation and visualization of individual control or homozygous mutant cells in a heterozygous genetic environment. Among its diverse applications, MADM has been used to dissect cell-autonomous gene functions important for cortical development and neural development in general.
View Article and Find Full Text PDFMapping the landscape of lineage-specific dynamic regulation of gene expression using single-cell transcriptomics and application to genetics of complex disease.
HGG Adv
December 2024
Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Clare Hall, University of Cambridge, Cambridge, England. Electronic address:
Single-cell transcriptome data can provide insights into how genetic variation influences biological processes involved in human biology and disease. However, the identification of gene-level associations in distinct cell types faces several challenges, including the limited reference resource from population scale studies, data sparsity in single-cell RNA sequencing, and the complex cell state pattern of expression within individual cell types. Here we develop genetic models of cell type specific and cell state adjusted gene expression in mid-brain neurons in the process of specializing from induced pluripotent stem cells.
View Article and Find Full Text PDFRevealing and mitigating the inhibitory effect of serotonin on HRP-mediated protein labelling.
Sci Rep
December 2024
Neurobiology Division, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Proximity-dependent biotinylation coupled with mass spectrometry enables the characterization of subcellular proteomes. This technique has significantly advanced neuroscience by revealing sub-synaptic protein networks, such as the synaptic cleft and post-synaptic density. Profiling proteins at this detailed level is essential for understanding the molecular mechanisms of neuronal connectivity and transmission.
View Article and Find Full Text PDFHigh-throughput gene expression analysis with TempO-LINC sensitively resolves complex brain, lung and kidney heterogeneity at single-cell resolution.
Sci Rep
December 2024
BioSpyder Technologies, Inc., Carlsbad, CA, USA.
We report the development and performance of a novel genomics platform, TempO-LINC, for conducting high-throughput transcriptomic analysis on single cells and nuclei. TempO-LINC works by adding cell-identifying molecular barcodes onto highly selective and high-sensitivity gene expression probes within fixed cells, without having to first generate cDNA. Using an instrument-free combinatorial indexing approach, all probes within the same fixed cell receive an identical barcode, enabling the reconstruction of single-cell gene expression profiles across as few as several hundred cells and up to 100,000 + cells per sample.
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