Kirsten Crichton
A5087550117- Single-cell and spatial transcriptomics
- Neuroinflammation and Neurodegeneration Mechanisms
- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Cell Image Analysis Techniques
- RNA Research and Splicing
- Neurogenesis and neuroplasticity mechanisms
- Gene Regulatory Network Analysis
- Immune cells in cancer
- Neuroscience and Neural Engineering
- Genetic Neurodegenerative Diseases
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- Mitochondrial Function and Pathology
- Zebrafish Biomedical Research Applications
- Bioinformatics and Genomic Networks
Allen Institute
2019-2023
Allen Institute for Brain Science
2019-2023
Seattle University
2022
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...
Here we report the generation of a multimodal cell census and atlas mammalian primary motor cortex as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance collective knowledge...
The mammalian brain consists of millions to billions cells that are organized into many cell types with specific spatial distribution patterns and structural functional properties1-3. Here we report a comprehensive high-resolution transcriptomic cell-type atlas for the whole adult mouse brain. was created by combining single-cell RNA-sequencing (scRNA-seq) dataset around 7 million profiled (approximately 4.0 passing quality control), approximately 4.3 using multiplexed error-robust...
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 Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in brain 1–3 . With proliferation multi-omics datasets, a major challenge is to validate and integrate results into biological understanding cell-type organization. Here we generated transcriptomes epigenomes from more than 500,000 individual cells mouse primary motor cortex, structure that has an evolutionarily conserved role locomotion. We developed...
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,...
Variation in cytoarchitecture is the basis for histological definition of cortical areas. We used single cell transcriptomics and performed cellular characterization human cortex to better understand areal specialization. Single-nucleus RNA-sequencing 8 areas spanning structural variation showed a highly consistent makeup 24 subclasses. However, proportions excitatory neuron subclasses varied substantially, likely reflecting differences connectivity across primary sensorimotor association...
The mammalian brain is composed of millions to billions cells that are organized into numerous cell types with specific spatial distribution patterns and structural functional properties. An essential step towards understanding function obtain a parts list, i.e., catalog types, the brain. Here, we report comprehensive high-resolution transcriptomic type atlas for whole adult mouse was created based on combination two single-cell-level, whole-brain-scale datasets: single-cell RNA-sequencing...
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...
Abstract Single cell transcriptomics has transformed the characterization of brain identity by providing quantitative molecular signatures for large, unbiased samples populations. With proliferation taxonomies based on individual datasets, a major challenge is to integrate and validate results toward defining biologically meaningful types. We used battery single-cell transcriptome epigenome measurements generated BRAIN Initiative Cell Census Network (BICCN) comprehensively assess types in...
SUMMARY The isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles perception, cognition, emotion learning. Both contain multiple regions, for many of which cellular composition is still poorly understood. In this study, we used complementary single-cell RNA-sequencing approaches, SMART-Seq 10x, to profile ∼1.2 million cells covering all regions adult mouse formation, derived a cell type taxonomy comprising 379 transcriptomic types....
Abstract Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, genetic attributes. To better constrain definition neuronal types, we characterized transcriptomes and intrinsic physiological properties over 3,700 GABAergic mouse visual cortical neurons reconstructed local morphologies 350 those neurons. We found that most transcriptomic (t-types) occupy specific laminar positions within cortex, many t-types exhibit consistent...
The neocortex is disproportionately expanded in human compared to mouse, both its total volume relative subcortical structures and the proportion occupied by supragranular layers that selectively make connections within cortex other telencephalic structures. Single-cell transcriptomic analyses of mouse show an increased diversity glutamatergic neuron types pronounced gradients as a function cortical depth. To probe functional anatomical correlates this diversity, we describe robust Patch-seq...
The isocortex and hippocampal formation are two major structures in the mammalian brain that play critical roles perception, cognition, emotion learning. Using single-cell RNA-sequencing approaches, we profiled ~1.2 million cells covering all regions adult mouse formation. cell types organized hierarchically exhibit varying degrees of discrete or continuous variations. Such molecular relationships correlate strongly with spatial distribution patterns types, which can be region-specific,...
ABSTRACT We report the generation of a multimodal cell census and atlas mammalian primary motor cortex (MOp or M1) as initial product BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved morphological electrophysiological properties, cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance...
ABSTRACT Understanding the diversity of cell types in brain has been an enduring challenge and requires detailed characterization individual neurons multiple dimensions. To profile morpho-electric properties mammalian systematically, we established a single pipeline using standardized patch clamp recordings slices biocytin-based neuronal reconstructions. We built publicly-accessible online database, Allen Cell Types Database, to display these data sets. Intrinsic physiological morphological...
Abstract To elucidate cortical microcircuit structure and synaptic properties we present a unique, extensive, public physiology dataset analysis platform. Through its application, reveal principles that relate cell type to synapse intralaminar circuit organization in the mouse human cortex. The dynamics of excitatory synapses align with postsynaptic subclass, whereas inhibitory partly presynaptic subclass but considerable overlap. Despite these associations, are heterogeneous most...
Abstract Variation in cortical cytoarchitecture is the basis for histology-based definition of areas, such as Brodmann areas. Single cell transcriptomics enables higher-resolution characterization types human cortex, which we used to revisit idea canonical microcircuit and understand functional areal specialization. Deeply sampled single nucleus RNA-sequencing eight areas spanning structural variation showed highly consistent cellular makeup 24 coarse subclasses. However, proportions...
Neurons are frequently classified into distinct groups or cell types on the basis of structural, physiological, genetic attributes. To better constrain definition neuronal types, we characterized transcriptomes and intrinsic physiological properties over 3,700 GABAergic mouse visual cortical neurons reconstructed local morphologies 350 those neurons. We found that most transcriptomic (t-types) occupy specific laminar positions within cortex, many t-types exhibit consistent...