Rachel Dalley
A5088428080- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Neural dynamics and brain function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Congenital heart defects research
- Neuroscience and Neural Engineering
- Trypanosoma species research and implications
- Gene expression and cancer classification
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Biochemical and Molecular Research
- Bioinformatics and Genomic Networks
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Research on Leishmaniasis Studies
- Advanced Memory and Neural Computing
- Molecular Biology Techniques and Applications
- Neonatal and fetal brain pathology
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Epigenetics and DNA Methylation
- Functional Brain Connectivity Studies
- Cardiac electrophysiology and arrhythmias
- RNA regulation and disease
Allen Institute
2015-2024
Allen Institute for Brain Science
2014-2024
Center for Infectious Disease Research
2007-2011
Abstract The primary motor cortex (M1) is essential for voluntary fine-motor control and functionally conserved across mammals 1 . Here, using high-throughput transcriptomic epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys mice, we demonstrate a broadly cellular makeup this region, with similarities that mirror evolutionary distance are consistent between the transcriptome epigenome. core molecular identities neuronal non-neuronal cell types allow us to...
Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, their relationships to histologic features routinely used for diagnosis unclear. We present the Ivy Atlas, anatomically based transcriptional atlas of human glioblastoma aligns individual with genomic alterations gene expression patterns, thus assigning information most important morphologic hallmarks tumor. its clinical database freely accessible online data...
ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present first digital atlas to incorporate neuroimaging, high‐resolution histology, chemoarchitecture across a complete adult female brain, consisting magnetic resonance imaging (MRI), diffusion‐weighted (DWI), 1,356...
Abstract Dendritic and axonal morphology reflects the input output of neurons is a defining feature neuronal types 1,2 , yet our knowledge its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on brain-wide scale, we established pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration analysis. We fully reconstructed 1,741 from cortex, claustrum, thalamus, striatum other brain regions in mice. identified 11 major...
We present a unique, extensive, and open synaptic physiology analysis platform dataset. Through its application, we reveal principles that relate cell type to properties intralaminar circuit organization in the mouse human cortex. The dynamics of excitatory synapses align with postsynaptic subclass, whereas inhibitory synapse partly presynaptic subclass but considerable overlap. Synaptic are heterogeneous most subclass-to-subclass connections. two main axes heterogeneity strength...
Abstract The neocortex is disproportionately expanded in human compared with mouse 1,2 , both its total volume relative to subcortical structures and the proportion occupied by supragranular layers composed of neurons that selectively make connections within other telencephalic structures. Single-cell transcriptomic analyses show an increased diversity glutamatergic neuron types pronounced gradients as a function cortical depth 3 . Here, probe functional anatomical correlates this diversity,...
Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to high diversity more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology single-cell RNA sequencing) sampling in human brain slices was used reliably target and analyze individual This characterization elucidated transitions between PVALB SST subclasses, morphological heterogeneity within...
Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion human neocortex marked by distinctive pyramidal neurons with extensive L1 branching, but whether interneurons are similarly diverse underexplored. Using Patch-seq recordings from neurosurgical tissue, we identified four transcriptomic subclasses mouse homologs, along distinct subtypes types...
Alzheimer's disease (AD) is the leading cause of dementia in older adults. Although AD progression characterized by stereotyped accumulation proteinopathies, affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from BRAIN Initiative to study middle temporal gyrus cell types 84 donors with varying pathologies. This cohort includes 33 male 51 female donors, an average age at time death 88 years. We used quantitative neuropathology...
The composition of the large, single, mitochondrion (mt) Trypanosoma brucei was characterized by MS (2-D LC-MS/MS and gel-LC-MS/MS) analyses. A total 2897 proteins representing a substantial proportion procyclic form cellular proteome were identified, which confirmed validity vast majority gene predictions. data also showed that genes annotated as hypothetical (species specific) overpredicted virtually all hypothetical, unlikely are not expressed. By comparing with genome sequence, 40...
As more people live longer, age-related neurodegenerative diseases are an increasingly important societal health issue. Treatments targeting specific pathologies such as amyloid beta in Alzheimer's disease (AD) have not led to effective treatments, and there is increasing evidence of a disconnect between traditional pathology cognitive abilities with advancing age, indicative individual variation resilience pathology. Here, we generated comprehensive neuropathological, molecular,...
The underlying pathology of schizophrenia (SZ) is likely as heterogeneous its symptomatology. A variety cortical and subcortical regions, including the prefrontal cortex, have been implicated in pathology, a number genes identified risk factors for disease development. We used situ hybridization (ISH) to examine expression 58 dorsolateral cortex (DLPFC, comprised Brodmann areas 9 46) from 19 individuals with premorbid diagnosis SZ 33 control individuals. Genes were selected based on: (1)...
Abstract The primary motor cortex (M1) is essential for voluntary fine control and functionally conserved across mammals. Using high-throughput transcriptomic epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, mouse, we demonstrate a broadly cellular makeup this region, whose similarity mirrors evolutionary distance consistent between the transcriptome epigenome. core molecular identity neuronal non-neuronal types allowed generation cross-species consensus cell...
Alzheimer's disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation protein aggregates, but underlying molecular cellular mechanisms driving AD progression vulnerable cell populations affected by remain coarsely understood. The current study harnesses single spatial genomics tools knowledge from BRAIN Initiative Cell Census Network to understand impact on middle temporal gyrus types. We...
Abstract Alzheimer’s disease (AD) is the most common cause of dementia in older adults. Neuropathological and imaging studies have demonstrated a progressive stereotyped accumulation protein aggregates, but underlying molecular cellular mechanisms driving AD progression vulnerable cell populations affected by remain coarsely understood. The current study harnesses single spatial genomics tools knowledge from BRAIN Initiative Cell Census Network to understand impact on middle temporal gyrus...
African trypanosomes, early diverged eukaryotes and the agents of sleeping sickness, have several basic cellular processes that are remarkably divergent from those in their mammalian hosts. They large mitochondria switch between oxidative phosphorylation glycolysis as major pathways for energy generation during life cycle. We report here identification characterization multiprotein mitochondrial complexes procyclic form Trypanosoma brucei. These were identified purified using a panel...
The mitochondrial F0F1 ATP synthase is an essential multi-subunit protein complex in the vast majority of eukaryotes but little known about its composition and role Trypanosoma brucei, early diverged eukaryotic pathogen. We purified by a combination affinity purification, immunoprecipitation blue-native gel electrophoresis characterized function. identified 22 proteins which five are related to F1 subunits, three F0 14 have no obvious homology outside kinetoplastids. RNAi silencing...
The neurogenic potential of the subgranular zone (SGZ) hippocampal dentate gyrus is likely to be regulated by molecular cues arising from its complex heterogeneous cellular environment. Through transcriptome analysis using laser microdissection coupled with DNA microarrays, in combination genome-wide situ hybridization data, we identified 363 genes selectively enriched adult mouse SGZ. These reflect expression different constituent cell types, including progenitor and dividing cells,...
The Patch-seq approach is a powerful variation of the patch-clamp technique that allows for combined electrophysiological, morphological, and transcriptomic characterization individual neurons. To generate datasets at scale, we identified refined key factors contribute to efficient collection high-quality data. We developed electrophysiology software with analysis functions specifically designed automate acquisition online quality control. recognized importance extracting nucleus success...