Showing papers by "Owen White published in 2021"
Allen Institute for Brain Science1, Harvard University2, University of California, San Diego3, Salk Institute for Biological Studies4, University of Washington5, Cold Spring Harbor Laboratory6, Leiden University Medical Center7, J. Craig Venter Institute8, United States Department of Veterans Affairs9, University of Maryland, Baltimore10, University of Maryland, College Park11, Ludwig Institute for Cancer Research12, Discovery Institute13, University of Connecticut14, Karolinska Institutet15, Washington University in St. Louis16, Icahn School of Medicine at Mount Sinai17, Delft University of Technology18, Harborview Medical Center19, University of California, Los Angeles20, Broad Institute21, La Jolla Institute for Allergy and Immunology22, Massachusetts Institute of Technology23, McGovern Institute for Brain Research24
TL;DR: The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals using high-throughput transcriptomic and epigenomic profiling of more than 450k single nuclei in humans, marmoset monkeys and mice as mentioned in this paper.
Abstract: The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
219 citations
Allen Institute for Brain Science1, Salk Institute for Biological Studies2, University of California, San Diego3, Cold Spring Harbor Laboratory4, University of Maryland, Baltimore5, Ghent University6, University of California, Berkeley7, Broad Institute8, California Institute of Technology9, University of Maryland, College Park10, Johns Hopkins University11, Harvard University12, Ludwig Institute for Cancer Research13, University of California, Los Angeles14, University of California, San Francisco15, University of Padua16, Washington University in St. Louis17, Howard Hughes Medical Institute18, University of Michigan19
TL;DR: In this paper, a reference atlas of diverse neuronal and non-neuronal cell types in the mouse primary motor cortex is presented, including a population of excitatory neurons that resemble pyramidal cells in layer 4.
Abstract: Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1-3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.
103 citations
TL;DR: The gEAR portal as discussed by the authors is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing for RNA-seq data, from multiple species, time points and tissues in a single-page, user-friendly browsable format.
Abstract: The gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets for de novo analysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.
78 citations