Showing 2021 papers, sorted by Most cited. Showing 25 of 39,449.
10.1016/j.cell.2021.04.021
The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion, and learning. We profiled ∼1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic cell-type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Contrary to…
10.1126/science.abf4588
Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in s…
Comparative cellular analysis of motor cortex in human, marmoset and mouse
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…
Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxid…
Epub 2021 Jun 7. Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8(+) T cells in tumors. Xu S(1), Chaudhary O(2), Rodríguez-Morales P(1), Sun X(3), Chen D(1), Zappasodi R(4), Xu Z(5), Pinto AFM(6), Williams A(7), Schulze I(4), Farsakoglu Y(1), Varanasi SK(1), Low JS(8), Tang W(3), Wang H(9), McDonald…
CADD-Splice—improving genome-wide variant effect prediction using deep learning…
Splicing of genomic exons into mRNAs is a critical prerequisite for the accurate synthesis of human proteins. Genetic variants impacting splicing underlie a substantial proportion of genetic disease, but are challenging to identify beyond those occurring at donor and acceptor dinucleotides. To address this, various methods aim to predict variant effects on s…
Survey of spiking in the mouse visual system reveals functional hierarchy.
The anatomy of the mammalian visual system, from the retina to the neocortex, is organized hierarchically1. However, direct observation of cellular-level functional interactions across this hierarchy is lacking due to the challenge of simultaneously recording activity across numerous regions. Here we describe a large, open dataset-part of the Allen Brain Obs…
10.1038/s41586-021-03950-0
Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morph…
Spatially resolved cell atlas of the mouse primary motor cortex by MERFISH
A mammalian brain is composed of numerous cell types organized in an intricate manner to form functional neural circuits. Single-cell RNA sequencing allows systematic identification of cell types based on their gene expression profiles and has revealed many distinct cell populations in the brain<sup>1,2</sup>. Single-cell epigenomic profiling<sup>3,4</sup> f…
Fine-Grained Entity Recognition
Entity Recognition (ER) is a key component of relation extraction systems and many other natural-language processing applications. Unfortunately, most ER systems are restricted to produce labels from to a small set of entity classes, e.g., person, organization, location or miscellaneous. In order to intelligently understand text and extract a wide range of i…
Expansion sequencing: Spatially precise in situ transcriptomics in intact biolo…
Methods for highly multiplexed RNA imaging are limited in spatial resolution and thus in their ability to localize transcripts to nanoscale and subcellular compartments. We adapt expansion microscopy, which physically expands biological specimens, for long-read untargeted and targeted in situ RNA sequencing. We applied untargeted expansion sequencing (ExSeq)…
Phenotypic variation of transcriptomic cell types in mouse motor cortex
Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties<sup>1,2</sup>. Most existing neural taxonomies are based on either transcriptomic<sup>3,4</sup> or morpho-electric<sup>5,6</sup> criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same…
A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain<sup>1-3</sup>. 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 epige…
Single-cell lineage tracing of metastatic cancer reveals selection of hybrid EM…
The underpinnings of cancer metastasis remain poorly understood, in part due to a lack of tools for probing their emergence at high resolution. Here we present macsGESTALT, an inducible CRISPR-Cas9-based lineage recorder with highly efficient single-cell capture of both transcriptional and phylogenetic information. Applying macsGESTALT to a mouse model of me…
Cellular anatomy of the mouse primary motor cortex
An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted<sup>1</sup>. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-…
Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chr…
Single-cell measurements of cellular characteristics have been instrumental in understanding the heterogeneous pathways that drive differentiation, cellular responses to signals, and human disease. Recent advances have allowed paired capture of protein abundance and transcriptomic state, but a lack of epigenetic information in these assays has left a missing…
Embryo-scale, single-cell spatial transcriptomics
Spatial patterns of gene expression manifest at scales ranging from local (e.g., cell-cell interactions) to global (e.g., body axis patterning). However, current spatial transcriptomics methods either average local contexts or are restricted to limited fields of view. Here, we introduce sci-Space, which retains single-cell resolution while resolving spatial…
Precise genomic deletions using paired prime editing
Current methods to delete genomic sequences are based on clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 and pairs of single-guide RNAs (sgRNAs), but can be inefficient and imprecise, with errors including small indels as well as unintended large deletions and more complex rearrangements. In the present study, we describe a prime edit…
Explaining Answers with Entailment Trees
Our goal, in the context of open-domain textual question-answering (QA), is to explain answers by showing the line of reasoning from what is known to the answer, rather than simply showing a fragment of textual evidence (a “rationale”). If this could be done, new opportunities for understanding and debugging the system’s reasoning become possible. Our approa…
The Ever-Increasing Array of Novel Inborn Errors of Immunity: an Interim Update…
The most recent updated classification of inborn errors of immunity/primary immunodeficiencies, compiled by the International Union of Immunological Societies Expert Committee, was published in January 2020. Within days of completing this report, it was already out of date, evidenced by the frequent publication of genetic variants proposed to cause novel inb…
Enhancer viruses for combinatorial cell-subclass-specific labeling
Rapid cell type identification by new genomic single-cell analysis methods has not been met with efficient experimental access to these cell types. To facilitate access to specific neural populations in mouse cortex, we collected chromatin accessibility data from individual cells and identified enhancers specific for cell subclasses and types. When cloned in…
EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organi…
Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion-Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational p…
Functional enhancer elements drive subclass-selective expression from mouse to…
Viral genetic tools that target specific brain cell types could transform basic neuroscience and targeted gene therapy. Here, we use comparative open chromatin analysis to identify thousands of human-neocortical-subclass-specific putative enhancers from across the genome to control gene expression in adeno-associated virus (AAV) vectors. The cellular specifi…
["Animals""Astrocytes""Dependovirus""Genetic Therapy"Making the hard problem of consciousness easier
Championing open science, an adversarial collaboration aims to unravel the footprints of consciousness
Relationship between simultaneously recorded spiking activity and fluorescence…
Fluorescent calcium indicators are often used to investigate neural dynamics, but the relationship between fluorescence and action potentials (APs) remains unclear. Most APs can be detected when the soma almost fills the microscope's field of view, but calcium indicators are used to image populations of neurons, necessitating a large field of view, generatin…
Perceptual awareness negativity: a physiological correlate of sensory conscious…
2021 Jun 23. Perceptual awareness negativity: a physiological correlate of sensory consciousness. Dembski C(1), Koch C(2), Pitts M(1).