Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses I
By onThis dataset provides a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Single nucleus RNA sequencing of SNr neurons
By onThese findings provide a unifying logic for how the developmental specification of diverse SNr neurons relates to the anatomical organization of basal ganglia circuits controlling specialized downstream brain regions.
Single-cell RNA-sequencing data from A Vulnerable Subtype of Dopaminergic Neurons Drives Early Motor Deficits in Parkinson’s Disease
By onSingle-nucleus RNA profiling of the ventral midbrain of MitoPark mice, their littermate controls and C57BL/6 mice at 8, 16, and 24 weeks of age (8 mice in each group; 4 males and 4 females).
Key Resource Table for Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses
By onComprehensive key resource table for the publication: "Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses", Mendelsohn et al 2025.
A prebiotic diet modulates microglia response and motor deficits in α-synuclein overexpressing mice
By onSingle-cell RNA-seq analysis of microglia from the substantia nigra and striatum uncovers increased pro-inflammatory signaling and reduced homeostatic responses in ASO mice compared to wild-type counterparts on standard diets. However, prebiotic feeding reverses pathogenic microglial states in ASO mice and promotes expansion of protective disease-associated macrophage (DAM) subsets of microglia. Notably, depletion of microglia using a CSF1R inhibitor eliminates the beneficial effects of prebiotics by restoring motor deficits to ASO mice despite feeding a prebiotic diet. These studies uncover a novel microglia-dependent interaction between diet and motor symptoms in mice, findings that may have implications for neuroinflammation and PD.
Datasets associated with “Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology”
By onDataset associated with the publication "Peripheral Neuronal Activation Shapes the Microbiome and Alters Gut Physiology"
A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain
By onWe report 690K single-cell transcriptomes from nine different brain regions from adult mice (Frontal and Posterior Cortex, Hippocampus, Thalamus, Cerebellum, Striatum, Globus Pallidus externus/Nucleus Basalis, Entopeduncular / Subthalamic Nuclei, & Substantia Nigra / Ventral Tegmental Area).
circRNA dataset
By onNew data set on circRNA in laser-captured neuron samples from 190 human brains of healthy controls, prodromal PD, and clinical PD (Dong et al., Nature Communications, in press). The RNA-seq raw FASTQ data and normalized expression matrix of all circRNAs in this study have been deposited in GEO under accession number GSE218203.
Hydrop enables droplet-based single-cell ATAC-seq and single-cell RNA-seq using dissolvable hydrogel beads
By onHyDrop protocol enables single-cell sequencing for RNA and chromatin accessibility. Generated over 7996 single-cell profiles for ATAC-seq and 9508 for RNA-seq in mouse cortex. Protocol validated on low-input samples from Drosophila brain.
SpatialBrain.org – a platform to view integrated data from Wade-Martins Laboratory of Molecular Neurodegeneration
By onAn open repository to access data and results from spatial and translatome expression profiling of basal dopaminergic neurons in mice (OVX and aging). More information can be viewed in published article Kilfeather & Khoo, et al. (2023) "Single-cell spatial transcriptomic and translatomic profiling of dopaminergic neurons in health, aging, and disease" Spatial Transcriptomic Analyses: - Cell Type Markers - SN/VTA Markers in Dopaminergic Neurons - Cell Number Changes in Age TRAP Analyses: - Dopaminergic Markers - Dopaminergic Ageing - Alternative Splicing in Dopaminergic Neurons Coming soon: Integration with iPS-derived dopaminergic transcriptomic datasets.
Single cell transcriptomics from DAT-Cre mouse gut tissue
By onColonic myenteric cells were dissociated, and live tdTomato-positive cells were FACS-collected. Colons were isolated from 2 male and female wild type adult DAT-Cre mice. Wild type C57Bl6/J was used as control for gating. Cells were processed according to 10X Genomics Chromium single cell 3' Reagent guidelines.
Subcellular and regional localization of mRNA translation in midbrain dopamine neurons
By onLocal translation within excitatory and inhibitory neurons is known to be involved in neuronal development and synaptic plasticity. Despite the extensive dendritic and axonal arborizations of monoaminergic neurons, the subcellular localization of protein synthesis has not been well-characterized in these populations. Here, we investigated mRNA localization in midbrain dopaminergic (mDA) neurons, cells with enormous axonal and dendritic projections, both of which can release dopamine (DA). Using highly-sensitive sequencing and imaging approaches in mDA axons, we found no evidence for axonal mRNA localization or translation. In contrast, we found that mDA neuronal dendritic projections into the substantia nigra reticulata (SNr) contain ribosomes and mRNAs encoding the DA synthesis, release, and reuptake machinery. Surprisingly, we found dendritic localization of mRNAs encoding synaptic vesicular release proteins in mDA neurons. Our results are consistent with a role for local translation in the regulation of DA transmission from dendrites, but not striatal axons. Finally, we defined a molecular signature of sparse mDA neurons in the SNr, including enrichment of an ER calcium pump previously undescribed in mDA neurons. RNA-sequencing of brain tissue, RiboTagged dopamine neurons, and synaptosomes using PLATE-seq 3'-tag sequencing or Clontech SMARTer full-length RNA library preparation This dataset is a part of "Subcellular and regional localization of mRNA translation in midbrain dopamine neurons" (Hobson et. al, 2022).
Pseudogenes limit the identification of novel common transcripts generated by their parent genes
By onGenomic sequences with high sequence similarity cause short sequencing reads to align to multiple locations, thus complicating genomic analyses. The authors investigated the impact of pseudogenes on transcriptomic analyses.
Examining the brain’s response to intestinal permeability and inflammation in the dextran sulfate sodium-induced colitis model.
By onMice were treated with DSS under various schedules to study colitis. Tissues from colon and brain regions were analyzed using RNA sequencing to understand molecular changes linked to gut leakiness and colitis progression.
Generation of Locus Coeruleus Norepinephrine Neurons from Human Pluripotent Stem Cells
By onCentral norepinephrine (NE) neurons, mainly located in the Locus coeruleus (LC), play roles in a wide range of behavioral and physiological processes. How the human LC-NE neurons develop and what roles they play in the pathophysiology of human diseases is poorly understood, partly due to the unavailability of functional human LC-NE neurons. Here we established a technology for efficient generation of LC-NE neurons from human pluripotent stem cells by identifying a novel role of ACTIVIN A in regulating the LC-NE transcription factors in the dorsal rhombomere 1 (r1) progenitors. The in vitro generated human LC-NE neurons not only display extensive axonal arborization and release/uptake NE, but also exhibit the pacemaker activity, calcium oscillation, and in particular chemoreceptor activity in response to CO2. Multiple timepoint single nucleus RNA-Seq (snRNA-Seq) analysis captured the dynamic NE differentiation process, confirmed the NE cell population and revealed the differentiation trajectory from hindbrain progenitors to NE neurons via ASCL1 expressing precursor stage. The LC-NE neurons engineered with a NE sensor reliably reported the extracellular NE level. The availability of functional human LC-NE neurons enables investigation of their roles in the pathogenesis of and development of therapeutics for neural psychiatric and degenerative diseases.
Targeted long-read RNA-seq
By onTargeted long-read RNAseq of SNCA, GBA1, and GBAP1. Three datasets are available: (i) human brain (ii) iPSC-derived astrocytes microglia neurons and (iii) iPSC-derived midbrain dopaminergic neurons.
Parkinson’s Disease MAGMA Analysis Ranked Genes
By onGWAS summary statistics for PD risk were obtained and processed using the MAGMA tool on FUMA’s online platform to generate a scored list (z-scores) of significant genes.
MERFISH Dataset of Mouse Dopamine Neurons
By onMERFISH runs of mouse Midbrain spatial transcriptomics
Primary data associated with the manuscript “Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2-driven and idiopathic Parkinson’s disease” (doi: 10.1073/pnas.2402206121)
By onPrimary data (RNA sequencing; microscopy& imaging) for the manuscript (doi: 10.1073/pnas.2402206121), including a ReadMe file (with description of the data and file structure).
snRNA data from Gaertner & Oram et al., 2024
By onDAT-Cre mice with a nuclear GFP reporter and either WT or heterozygous G2019S mutant alleles for the gene Lrrk2. Samples contain tissue from midbrains after isolation of DAT+ nuclei via microfluidic sorting for GFP.
