Cited by 481Single-cell and spatial transcriptomicsCell Image Analysis TechniquesDevelopmental Biology and Gene Regulation

What is a cell type and how to define it?

Open access
Zeng, Hongkui·2022·Cell

Abstract

Cell types are the basic functional units of an organism. They exhibit diverse phenotypic properties at multiple levels, making them challenging to define, categorize and understand. This Review provides an overview of the basic principles of cell types rooted in evolution and development, and discusses approaches to characterize and classify cell types and investigate how they contribute to the organism’s function, using the mammalian brain as a primary example. I propose a roadmap towards a conceptual framework and knowledge base of cell types that will enable a deeper understanding of the dynamic changes of cellular function under healthy and diseased conditions.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that cell types arise through evolution and have identities encoded in the genome, and it proposes a multilevel, iterative roadmap anchored in single-cell transcriptomic taxonomy and refined by epigenomic, spatial, anatomical, physiological, functional, developmental, and cross-species evidence. It illustrates these ideas mainly with the mammalian brain, especially mouse cortex.

Key findings

  • Single-cell transcriptomic taxonomies in adult mammalian brain are consistently hierarchical: neuronal versus non-neuronal classes at the top, then major brain structures/regions, then subclasses and types; in mouse cortex, glutamatergic neurons divide into nine subclasses and GABAergic neurons into six, giving about 110 transcriptomic types per cortical area.
  • Transcriptomic types correspond well with spatial organization and some multimodal properties: mouse retina studies converge on roughly 130 neuron types, cortical transcriptomic continua align with laminar depth, and Patch-seq/MERFISH link transcriptomic variation to morphology, electrophysiology, and layer position.
  • Cell types must be distinguished from cell states; transcriptomic snapshots can mix transient states with stable identities, and non-neuronal cells such as astrocytes, oligodendrocytes, microglia, and vascular cells show pronounced state changes across development, aging, injury, and disease.
  • The proposed roadmap is to use transcriptomic taxonomy as an anchor, add epigenomic and spatial transcriptomic data, integrate anatomy, physiology, connectivity, and function with molecular identification, study development and cross-species evolution, and organize results in a branching, tree-like classification with standardized ontology and nomenclature.

Methods

  • Design: conceptual review and synthesis, not a primary empirical study; no new sample or dataset is reported.
  • Evidence base: literature on cell-type characterization across molecular, morphological, physiological, functional, developmental, and evolutionary modalities, with the mammalian brain and mouse cortex as main examples.
  • Analysis: narrative integration of single-cell transcriptomics, epigenomics, spatially resolved transcriptomics, Patch-seq, connectomics, lineage/trajectory studies, and cross-species comparisons; concludes with a proposed roadmap.

Limitations

  • The paper states that no consistent standard definition of cell types exists; it is often unclear whether types defined by different phenotypic features agree, and transcriptomic clusters at the lowest hierarchical levels have not been fully validated.
  • It notes technical and conceptual gaps: continuous variation makes exact type counts difficult; cross-species comparisons need well-annotated genomes, comparable ontologies, and high-quality data; single-cell proteomics and mammalian connectomics remain under development; links between transcriptomic types and projection or functional properties are unresolved.
  • Evident from the text: as a review, it presents no new experimental tests of its roadmap, and its examples are heavily weighted toward mammalian brain and mouse cortex, so generality to other organs and species is asserted rather than demonstrated.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cell.2022.06.031

Cites

216 of 216 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 60 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Within each cortical excitatory subclass, individual neurons show extensive heterogeneity along regional, topographic, and individual (potentially stochastic) axes.

    “Within each subclass, the study also finds extensive heterogeneity among individual neurons; this heterogeneity reflects three axes of variations: regional specificity, topographic specificity and individual (potentially stochastic) variation,”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Peng et al., 2021 source

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  • Premisecitation

    In mouse visual cortex, visual response properties such as orientation or direction selectivity differ only at subclass level.

    “Using the former approach, it has been shown that GABAergic transcriptomic types in mouse visual cortex differ in their response to behavioral states (e.g., running versus resting), whereas visual response properties (e.g., orientation or direction selectivity) only differ at subclass level (Bugeon et al., 2021);”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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  • Interpretationreasoning

    Single-cell transcriptomics and connectomics are the two main approaches that could achieve complete cell type definition.

    “Currently single-cell transcriptomics and connectomics (i.e., delineating the patterns of interconnections between individual neurons) are the two primary approaches that have the potential to meet the completeness requirement.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Patch-seq data integrating transcriptome, electrophysiology and morphology indicate that mouse motor cortex cell types have corresponding multimodal distinctions at the subclass level.

    “Integration of transcriptomic, electrophysiological and morphological properties by Patch-seq reveals multimodal corresponding distinctions of mouse motor cortex cell types at subclass level (Scala et al., 2021).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Scala et al., 2021 source

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  • Premisecitation

    These three axes of variation do not readily correlate with transcriptomic types within the subclass.

    “which do not readily correlate with transcriptomic types within the subclass.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Peng et al., 2021 source

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    Interpretationreasoning

    Single-cell transcriptomics alone can faithfully capture overall cell type organization at class and subclass levels, but validity at the lowest branch level remains untested.

    “suggesting that single-cell transcriptomics alone can faithfully capture the overall cell type organization at class and subclass levels, although the validity of transcriptomic clusters at the lowest branch level has yet to be fully tested.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Glutamatergic neuron types differ between visual and motor cortical areas, while GABAergic neuron types are shared between these areas.

    “Glutamatergic neuron types are distinct between visual and motor cortical areas whereas GABAergic neuron types are shared between the two areas (Tasic et al., 2018).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Interpretationnone given

    Whether specific transcriptomic types beyond the subclass level have specific connectional or functional attributes is still unclear in many cases.

    “At the same time, whether specific transcriptomic types (beyond the subclass level) have specific connectional or functional attributes or not is still unclear in many cases.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationreasoning

    A single-target-site Retro-seq assay is often insufficient to resolve a transcriptomic type's target specificity except in special cases, because a neuron type usually has multiple projection targets and a neuron within that type can choose a subset specifically or randomly.

    “Since a neuron type usually has multiple projection targets and a neuron within that type can choose a subset of those targets either specifically or randomly, a single-target-site Retro-seq assay is often insufficient to resolve the target specificity of a transcriptomic type except in special cases.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: A neuron type usually has multiple projection targets and individual neurons can choose a subset specifically or randomly.
  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Some connectional or functional properties should not be used to define cell types because they may be emerging properties from network interactions or experience/activity-dependent processes representing cell state rather than type.

    “it is also reasonable to propose that some connectional or functional properties should not be used to define cell types, because they may be emerging properties arising from the interaction of a network of cell types, or from experience and/or activity dependent processes that represent a cell “state” rather than a defining feature for a cell “type”.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Specific molecular signatures responsible for certain essential anatomical or functional features may be hidden below noise and need supervised approaches to be brought out.

    “specific molecular signatures responsible for certain essential anatomical or functional features may be hidden below noise and will need to be brought out through supervised approaches and used to refine the classification of cell types towards more functional relevance.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Interpretationnone given

    Cell types are products of evolution, and their identities are encoded in the genome.

    “Therefore, the first and foremost principle is that cell types are the product of evolution and cell type identities are encoded in the genome.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    Transcriptomic clusters can in theory be infinitely subdivided, and profiling more cells yields more clusters.

    “since in theory transcriptomic clusters can be infinitely subdivided and the more cells profiled the more clusters can be obtained”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    A study using complete reconstruction in cortical excitatory neuron subclass-specific Cre driver lines found distinct projection patterns between subclasses, including between IT and ET and between L2/3 IT and L5 IT neurons, confirming subclass level projection specificity.

    “A study using this approach in cortical excitatory neuron subclass-specific Cre driver lines (Peng et al., 2021) reveals distinct projection patterns between subclasses, e.g., not only between IT and ET but also between L2/3 IT and L5 IT neurons, confirming subclass level projection specificity (Fig. 3C).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Peng et al., 2021 source

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    Premisecitation

    To reduce heterogeneity at the individual type level, triple-modality MET types were defined at a granularity between transcriptomic subclasses and types.

    “To overcome heterogeneity at individual type level, a set of triple-modality MET types are defined at an intermediate level of granularity (between transcriptomic subclasses and types).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Gouwens et al., 2020 source

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    Premisecitation

    Cells within an organism can be grouped into types, with cells of a type sharing similar structure and function distinct from other types.

    “Studies over the past century have revealed that cells within an organism can be grouped into types – cells within a type exhibit similar structure and function that are distinct from cells in other types (Arendt, 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
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    Premisecitation

    Oligodendrocyte pathology is evident in multiple sclerosis, schizophrenia, and Alzheimer's disease.

    “Oligodendrocyte pathology is evident in a range of disorders including multiple sclerosis, schizophrenia and Alzheimer’s disease (Kuhn et al., 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation

    Developmental trajectory is not the same as developmental lineage; a progenitor can produce cells belonging to several neuronal and non-neuronal types, ordered by developmental timing.

    “Developmental trajectory also is not the same as developmental lineage, as a lineage is defined as all the cells descended from a single precursor/progenitor and it has been shown in multiple systems that a progenitor can produce cells belonging to several neuronal and non-neuronal types, ordered by developmental timing (Agathocleous and Harris, 2009; Sagner and Briscoe, 2019; Sulston et al., 1983”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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    • cites Sagner and Briscoe, 2019

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    • cites Sulston et al., 1983 source

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  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    The transcriptomic taxonomy contains evolutionarily rooted molecular signatures and allows effective label transfer and linking with all other modalities.

    “The transcriptomic taxonomy contains evolutionarily rooted molecular signatures and allows effective label transfer and linking with all other modalities.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.

    Interpretationnone given

    Cell types are the product of evolution and are the basic functional units of an organism.

    “In conclusion, cell types are the product of evolution, and they are the basic functional units of an organism.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Individual variations within a species driven by genetic or environmental factors may manifest as a variety of cell type or cell state variations.

    “Furthermore, individual variations within a species (e.g., within the human population) that are driven by genetic or environmental factors may be manifested as a variety of cell type or cell state variations.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Premisecitation

    Microglia display diverse and dynamic phenotypic states and play roles in development, adulthood, aging, and diseases.

    “Microglia display diverse and dynamic phenotypic states and play a plethora of roles in development, adulthood (homeostasis), aging and diseases (Butovsky and Weiner, 2018; Prinz et al., 2019; Thion and Garel, 2020).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Butovsky and Weiner, 2018 source

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    • cites Prinz et al., 2019 source

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    • cites Thion and Garel, 2020

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    Premisenone given

    The distinction between cell types and cell states is particularly challenging during development, as cells continually change their states and may switch their cell type identities at certain key time points.

    “The distinction between cell types and cell states is particularly challenging during development, as cells continually change their states and, at certain key time points, they may switch their cell type identities.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Premisecitation

    Opposing morphogen gradients establish the basic plan for cortex (anterior-posterior) or spinal cord (dorsal-ventral) patterning and provide instructive signals for expression of complementary transcription factor activators and repressors, which define distinct neural progenitor domains.

    “First, opposing morphogen gradients establish the basic plan for cortex (anterior-posterior) or spinal cord (dorsal-ventral) patterning and provide instructive signals for the expression of complementary sets of transcription factor activators and repressors, which in turn define distinct neural progenitor domains within cortex or spinal cord.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cadwell et al., 2019 source

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    • cites Catela et al., 2015 source

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    • cites Jessell, 2000 source

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    Premisecitation

    Extensive historical studies of mouse cortex and spinal cord cell types have uncovered several common principles.

    “The generation and patterning of mouse cortex and spinal cord cell types are two example systems where extensive historical studies have uncovered several common principles (Cadwell et al., 2019; Catela et al., 2015; Jessell, 2000; O’Leary et al., 2007; Osseward and Pfaff, 2019; Sagner and Briscoe, 2019).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cadwell et al., 2019 source

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    Premisecitation

    Myelination exhibits activity-dependent plasticity.

    “Myelination process also exhibits activity-dependent plasticity (Monje, 2018).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Monje, 2018 source

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  • Classified as probably not a substantial claim.

    Premisereasoning

    The transcriptomic taxonomy organizes cell types hierarchically, from major divisions at class and subclass levels to more granular and fuzzier divisions at type and subtype levels due to prevailing continuous variations at the latter levels.

    “The transcriptomic taxonomy organizes cell types in a hierarchical manner, laying out different levels of descriptions from major divisions at class and subclass levels to more granular and fuzzier divisions at type and subtype levels (due to the more prevailing continuous variations at the latter levels).”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Astrocytes exhibit diverse morphological and physiological properties in different brain regions and contribute to essential functions in blood-brain barrier, synaptogenesis, neurotransmitter buffering, ion homeostasis, and secretion of neuroactive agents.

    “Astrocytes exhibit diverse morphological and physiological properties in different brain regions and contribute to essential functions in blood-brain barrier, synaptogenesis, neurotransmitter buffering, ion homeostasis, and secretion of neuroactive agents (Ben Haim and Rowitch, 2017; Khakh and Deneen, 2019).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ben Haim and Rowitch, 2017

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    • cites Khakh and Deneen, 2019

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  • May combine two claims.

    Premisecitation

    The set of cell type-defining transcription factors in a progenitor or daughter cell can change with time, so different neuronal types emanate from the same progenitor in a precisely timed birth order.

    “The set of cell type-defining transcription factors in a progenitor or a daughter cell can change with time, such that different neuronal types emanate from the same progenitor in a precisely timed “birth order”.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cadwell et al., 2019 source

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    • cites Catela et al., 2015 source

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    • cites Jessell, 2000 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Later in development, the same neural progenitors also generate non-neuronal cell types such as astrocytes and oligodendrocytes.

    “Later in development, the same neural progenitors also generate non-neuronal cell types such as astrocytes and oligodendrocytes.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Cadwell et al., 2019 source

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    • cites Catela et al., 2015 source

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    Premisecitation

    Single-cell transcriptomic studies reveal a relatively homogeneous adult microglia population and greater heterogeneity of microglia states at different developmental stages, during aging, and in pathological conditions.

    “Single-cell transcriptomic studies reveal a relatively homogeneous adult microglia population, and greater heterogeneity of microglia states at different developmental stages, during aging and in pathological conditions (Hammond et al., 2019; Li et al., 2019; Masuda et al., 2019).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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    • cites Li et al., 2019

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    • cites Masuda et al., 2019 source

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    Premisecitation

    Reactive astrocytes undergo morphological, molecular, and functional changes in response to injury or CNS diseases and may adopt multiple heterogeneous states depending on context.

    “Reactive astrocytes undergo morphological, molecular, and functional changes in response to injury or CNS diseases; they may adopt multiple, heterogeneous states depending on context (Escartin et al., 2021).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Escartin et al., 2021 source

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27 of 27
  • The paper relies on this without support.

    Cell types are the basic functional units of an organism.

    “Cell types are the basic functional units of an organism.”
  • The paper relies on this without support.

    There has not been a consistent and standard definition of cell types.

    “However, there has not been a consistent and standard definition of cell types even though it is critical for reproducible investigation.”
  • The paper relies on this without support.

    It is often unclear whether cell types defined by different phenotypic features agree, nor which feature is the right one to define cell types.

    “It is often unclear if cell types defined by different phenotypic features agree with each other, nor which feature is the “right” one to define cell types.”
  • The paper relies on this without support.

    Cellular properties at individual cell level are highly heterogeneous, and variations in different modalities do not necessarily exhibit high concordance, making it often impossible to define exactly what is a cell type and draw clear boundaries between types.

    “At the same time, cellular properties at individual cell level are highly heterogeneous, variations in different modalities do not necessarily exhibit high degrees of concordance, making it often impossible to define exactly what is a cell type and draw clear boundaries between “types”.”
  • The paper relies on this without support.

    The vast majority of cortical and subcortical neuron types have long-range axon projections forming circuit networks throughout the brain.

    “The vast majority of cortical and subcortical neuron types have long-range axon projections to form circuit networks throughout the brain.”
  • The paper relies on this without support.

    Transcriptomes are rich in containing molecular correlates of all sorts of cellular properties.

    “Since transcriptomes are rich in containing the molecular correlates of all sorts of cellular properties”
  • The paper relies on this without support.

    Emergence of a new cell type during development is more often the consequence of cell division from which a daughter cell takes up a new cell type identity.

    “More often, emergence of a new cell type during development is the consequence of cell division from which a daughter cell takes up a new cell type identity (Fig. 4).”
  • The paper relies on this without support.

    Coordinated neuronal activities in brain circuits generate sensory perception and behavior.

    “Coordinated neuronal activities in brain circuits generate sensory perception and behavior.”
  • The paper relies on this without support.

    IEG activation leads to expression of downstream effectors, such as ion channels or synaptic proteins, that shape cell states and remodel neuronal connections.

    “IEG activation leads to expression of downstream effectors, such as ion channels or synaptic proteins, that shape the cell states and remodel neuronal connections.”
  • The paper relies on this without support.

    Cell state changes in the brain are closely related to neural plasticity.

    “Cell state changes in the brain are closely related to neural plasticity.”
  • The paper relies on this without support.

    Various diseased conditions can induce pathological changes in cell states in different brain regions or tissue organs.

    “Similarly, various diseased conditions can induce pathological changes in cell states in different brain regions or tissue organs.”
  • The paper relies on this without support.

    Numerous studies have revealed selective vulnerability of specific cell types for specific diseases.

    “Numerous studies have revealed selective vulnerability of specific cell types for specific diseases.”
  • The paper relies on this without support.

    Astrocytes become reactive under pathological conditions.

    “Astrocytes become reactive under pathological conditions.”
  • The paper relies on this without support.

    Oligodendrocytes are the myelinating cells of the CNS generated from OPCs throughout life.

    “Oligodendrocytes are the myelinating cells of the central nervous system (CNS) that are generated from OPCs throughout life.”
  • The paper relies on this without support.

    Microglia are the primary innate immune cells in the CNS and have a distinct developmental origin from peripheral immune cells.

    “Finally, microglia are the primary innate immune cells in the CNS and have a distinct developmental origin from peripheral immune cells.”
  • The paper relies on this without support.

    Microglia are generated from mesodermal progenitors that arise from the yolk sac and are among the earliest residential cell types in the brain.

    “They are generated from mesodermal progenitors that arise from the yolk sac and are among the earliest residential cell types in the brain.”
  • The paper relies on this without support.

    Microglia can be both responders to and inducers of various neurodegenerative, neuroinflammatory and neurodevelopmental diseases.

    “In particular, microglia can be both responders to and inducers of various neurodegenerative, neuroinflammatory and neurodevelopmental diseases.”
  • The paper relies on this without support.

    The entire repertoire of cell types is built through sequential and parallel developmental events starting from the zygote.

    “The entire repertoire of cell types in the brain and the body is built through a sequential and parallel series of spatially and temporally coordinated developmental events starting from a single fertilized egg, the zygote.”
  • The paper relies on this without support.

    Transcriptional and epigenetic regulatory programs are unfolded from genome sequences and drive proliferation and differentiation leading to diverse cellular phenotypes.

    “Transcriptional and epigenetic regulatory programs are unfolded from the genome sequences and drive a cascading series of cell proliferation and differentiation processes leading to the manifestation of diverse cellular phenotypes.”
  • The paper relies on this without support.

    Earlier-stage ancestral cell types are fewer and more multipotent, giving rise to more descendant cell types with increasingly restricted fates.

    “In the developmental ontogeny of cell types, earlier-stage ancestral cell types are fewer and are more multipotent, they give rise to a larger number of descendant cell types with increasingly restricted fates.”
  • The paper relies on this without support.

    The developmental program specifies a spatial plan, including the location of organs and the spatial organization of cell types.

    “The developmental program rolls out not only a temporal but also an elaborate spatial plan, specifying the location of each tissue organ and the spatial organization of all the cell types within each.”
  • The paper relies on this without support.

    Brain development includes patterning and regionalization, neurogenesis and neuronal migration, gliogenesis and glia differentiation, neuronal differentiation and circuit formation, and circuit refinement and plasticity.

    “For the brain, the main series of events of brain development leading to the mature adult-stage cell types and circuits include: patterning and regionalization (laying out the master plan of brain architecture), neurogenesis and neuronal migration, gliogenesis and glia cell differentiation, neuronal differentiation and circuit formation (axonogenesis, dendritic arborization, synaptogenesis, myelin”
  • The authors state this as an assumption.

    Transcriptomic changes tend to be more continuous during cell state transitions and more abrupt or discrete when cells switch their types.

    “Although not absolute, it is reasonable to assume that transcriptomic changes tend to be more continuous during cell state transitions, and more abrupt or discrete when cells switch their types.”
  • The paper relies on this without support.

    A neuron type usually has multiple projection targets and individual neurons can choose a subset specifically or randomly.

    “Since a neuron type usually has multiple projection targets and a neuron within that type can choose a subset of those targets either specifically or randomly”
24 of 24

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Recent studies define a cell type as a continuous set of cell states aligned with the range of cellular phenotypes resulting from interaction between the cell type and its microenvironment.

    “Recent studies define a cell type as a (continuous) set of cell states, which can be aligned with the range of cellular phenotypes resulting from the interaction between a cell type and its microenvironment4.”

    From Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation (2024) · cites this paper as [4]

    In “Cell types versus cell states” (page unavailable), the paper says a cell type can exist in different states, that states can respond to context, and that state transitions tend to be continuous. It does not define a cell type as a continuous set of states or equate that set with the range of phenotypes produced by interaction with its microenvironment. (LLM, conf=0.84)

    Experimental — accuracy not yet measured
  • Single-cell transcriptomics provides unprecedented profiling depth and scalability, enabling comprehensive quantitative analysis and classification of cell types at scale.

    “Single-cell transcriptomics by single-cell RNA sequencing (scRNA-seq) or single-nucleus RNA sequencing (snRNA-seq) provides unprecedented profiling depth and scalability, enabling comprehensive quantitative analysis and classification of cell types at scale2,3,7–9.”
  • Consistent with the principle of hierarchical cell-type organization identified in previous studies, the study defined a hierarchical taxonomy of cell types across the entire mouse brain with four levels: class, subclass, supertype and cluster.

    “Consistent with the principle of hierarchical cell-type organization identified in previous studies2, here we have defined a hierarchical taxonomy of cell types across the entire mouse brain, with four levels of classification: class, subclass, supertype and cluster (or type).”

Cites

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3 of the 219 references couldn’t be matched to a known paper.

Cited by

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Authors
Zeng, H.
Affiliations
Allen Institute for Brain Science (US)
Corresponding author
Zeng, Hongkui
Venue
Cell
Publisher
Elsevier BV
Published
2022-07
Volume
185
Issue
15
Pages
2739-2755
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4286449197
Cited by
439
References
219
Citations by year
2026: 95 · 2025: 126 · 2024: 121 · 2023: 83 · 2022: 13 · 2021: 1
FWCI
8.98
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIMH (U19MH114830)
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
cell types, cell type classification, mammalian brain, cell function, cellular heterogeneity
MeSH terms
Animals, Brain, Humans, Mammals, Single-Cell Analysis

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