Adult mouse cortical cell taxonomy revealed by single cell transcriptomics

Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz P.; Gray, Lucas T.; Sorensen, Staci A.; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya V.; Parry, Sheana; Lee, Changkyu; Smith, Kimberly A.; Bernard, Amy; Madisen, Linda; Sunkin, Susan M.; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

doi:10.1038/nn.4216

Cited by 1,563 publications

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References 78 publications

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“…Weighted gene co-expression network analysis (WGCNA) was performed to identify modules of co-expressed genes, and the genes were then used to cluster cell types, as described in previously ( Figure 4A) (Tasic et al, 2016;Thomsen et al, 2016). We observed 41 cell clusters-8 at D24, 11 at D54, 13 at D100 and 10 at D125-which showed clear separation between progenitor (Cit − ) and neuron (Cit + ) cells at each time point.…”

Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 65%

“…A similar reduction in SST cell percentages was observed between D54 (46.3 ± 6.1%, dark blue bar) and D100 (24.9 ± 4.5%, light blue bar). We quantified the expression of SST subtype markers CALB2, NR2F2 and TH ( Figure 1H, S1) (DeFelipe et al, 2013;Tasic et al, 2016). CALB2 + and NR2F2 + cell percentages decreased over time.…”

Section: In Vitro Generation Of Mge Progenitors and Neuronsmentioning

confidence: 99%

“…Multiple subtypes of SST + interneurons exist in adult cortex, but it remains unknown whether specification is a result of intrinsic or extrinsic influences (Ma et al, 2006;Tasic et al, 2016;Zeisel et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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SummaryGABAergic interneurons are essential for neural circuit function and their loss or dysfunction is implicated in human neuropsychiatric disease. In vitro methods for interneuron generation hold promise for studying human cellular and functional properties and ultimately therapeutic cell replacement. We describe here a protocol for generating cortical interneurons from hESCs and analyze the properties and maturation timecourse of cell types using single-cell RNAseq. We find that the cell types produced mimic in vivo temporal patterns of neuron and glial production, with immature progenitors and neurons observed early and mature cortical neurons and glial cell types produced late. By comparing the transcriptomes of immature interneurons to more mature neurons, we identified genes important for human interneuron differentiation. Many of these genes were previously implicated in neurodevelopmental and neuropsychiatric disorders. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access

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Section: Scrna-seq Analysis Of In Vitro-derived Human Interneuronsmentioning

confidence: 65%

Section: In Vitro Generation Of Mge Progenitors and Neuronsmentioning

confidence: 99%

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Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Close¹,

Yao²,

Miller³

et al. 2017

Neuron

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“…Indeed, Cardin et al (31) found that the optogenetic stimulation of PV cells increased γ-rhythms, reflecting the fine temporal dynamics. It should be noted that SST, PV, and VIP cells have multiple subclasses (3), and incorporating them into this model would be desirable.…”

Section: Systems-level Models: Three Levels Of Granularitymentioning

confidence: 99%

Inferring cortical function in the mouse visual system through large-scale systems neuroscience

Hawrylycz

Anastassiou

Arkhipov

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort.T he neocortical sheet is a layered structure with a thickness that varies by a factor of two to three, whereas its surface area varies by 50,000 between the small smoky shrew and the massive blue whale. A unique hallmark of mammals, neocortex is a highly versatile, scalable, ∼2D computational tissue that excels at real time sensory processing across modalities and making and storing associations as well as planning and producing complex motor patterns. Neocortex consists of smaller modular units (columnar circuits that reach across the depth of cortex) broadly repeated iteratively across the cortical sheet. These modules vary considerably in their connectivity and properties between regions, with some controversy whether there is, indeed, a single canonical function performed by any and all neocortical columns.A deep understanding of cortex necessitates measuring relevant biophysical variables, such as recording action and membrane potentials, and relating them to genetically identified cell types. Mapping, observing, and intervening in widespread but highly specific cellular activity are more readily accomplished in the mouse, Mus musculus, than in the human brain. The brain of the laboratory mouse is more than three orders of magnitude smaller than the human brain in weight (0.4 vs. 1,350 g) and contains 71 million vs. 86 billion nerve cells for the entire brain and 14 million vs. 16 billion nerve cells for neocortex (1).The Allen Institute for Brain Science is engaged in a 10-y, highthroughput, milestone-driven effort to characterize all cortical cell types for the mouse cortex to build a small number of distinct experimental and computational platforms, called brain observatories, for studying behaving mice and to construct abstract and biophysically realisti...

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“…single neuron | mass spectrometry | metabolism | patch clamp S ingle-cell genomic, proteomic, and metabolic studies have attracted increasing attention with the development of singlecell technologies, such as flow cytometry (1-3), single-cell PCR (4,5), single-cell RNA sequencing (6)(7)(8), immunofluorescence (9,10), and electrochemistry (11,12). Single-cell analysis has become increasingly important in biology, especially in neuroscience research, because neurons are specialized cells with a huge diversity of shapes, connections, and anatomical, electrophysiological, and biochemical properties (13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry

Zhu

Zou

Wang

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The use of single-cell assays has emerged as a cutting-edge technique during the past decade. Although single-cell mass spectrometry (MS) has recently achieved remarkable results, deep biological insights have not yet been obtained, probably because of various technical issues, including the unavoidable use of matrices, the inability to maintain cell viability, low throughput because of sample pretreatment, and the lack of recordings of cell physiological activities from the same cell. In this study, we describe a patch clamp/MS-based platform that enables the sensitive, rapid, and in situ chemical profiling of single living neurons. This approach integrates modified patch clamp technique and modified MS measurements to directly collect and detect nanoliter-scale samples from the cytoplasm of single neurons in mice brain slices. Abundant possible cytoplasmic constituents were detected in a single neuron at a relatively fast rate, and over 50 metabolites were identified in this study. The advantages of direct, rapid, and in situ sampling and analysis enabled us to measure the biological activities of the cytoplasmic constituents in a single neuron, including comparing neuron types by cytoplasmic chemical constituents; observing changes in constituent concentrations as the physiological conditions, such as age, vary; and identifying the metabolic pathways of small molecules.single neuron | mass spectrometry | metabolism | patch clamp

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Adult mouse cortical cell taxonomy revealed by single cell transcriptomics

Cited by 1,563 publications

References 78 publications

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Single-Cell Profiling of an In Vitro Model of Human Interneuron Development Reveals Temporal Dynamics of Cell Type Production and Maturation

Inferring cortical function in the mouse visual system through large-scale systems neuroscience

Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry

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