What is a cell type and how to define it?
Open accessAbstract
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.
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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.
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Cites
Statistics
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- cites Bugeon et al., 2021
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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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- Interpretationnone given
Transcriptomic types have excellent correspondence with their spatial distribution patterns.
“So far it has been shown that transcriptomic types have excellent correspondence with their spatial distribution patterns.”
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These visual cortex GABAergic MET types show strong cross-modality concordance and mutual predictability.
“These visual cortex GABAergic MET types show robust cross-modality concordance and mutual predictability.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gouwens et al., 2020 source
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- Premisecitation
In mouse somatosensory cortex, higher sensory response is seen in a specific L2/3 IT excitatory transcriptomic type.
“in somatosensory cortex, higher sensory response is seen in a specific L2/3 IT excitatory transcriptomic type (Condylis et al., 2022).”
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- Premisecitation
A Patch-seq study of mouse visual cortical GABAergic neurons found relatively high corresponding continuous variation of transcriptomic types with cortical-depth anatomical distribution and morpho-electrical properties.
“Another Patch-seq study of mouse visual cortical GABAergic neurons also reveals a relatively high degree of corresponding continuous variations of transcriptomic types with their anatomical distribution along the cortical depth and the variations of their morpho-electrical properties (Fig. 3B) (Gouwens et al., 2020).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gouwens et al., 2020 source
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- Premisecitation
In mouse visual cortex, GABAergic transcriptomic types differ in their response to behavioral states such as running versus resting.
“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 paperSubstantial claim0 of 1 sources checked- cites Bugeon et al., 2021
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- Premisecitation
In mouse hypothalamus, activated neurons during a specific behavioral state are often distributed across a range of transcriptomic cell types.
“In hypothalamus, several studies using either of the two approaches in mice demonstrate that activated neurons during a specific behavioral state are often distributed across a range of transcriptomic cell types (Kim et al., 2019; Moffitt et al., 2018; Xu et al., 2020).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation
Cell type-specific gene expression changes associated with different cell states may be seen during circadian cycles, variable metabolic states, development, aging, or under behavioral, pharmacological or diseased conditions.
“Cell type-specific gene expression changes associated with different cell states may be seen during circadian cycles, variable metabolic states, development, aging, or under behavioral, pharmacological or diseased conditions (Fig. 4) (Mayr et al., 2019; Morris, 2019).”
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Some transcriptomic types show extra heterogeneity in morpho-electrical properties.
“There is also additional heterogeneity of morpho-electrical properties within some transcriptomic types, indicating a more complex picture.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scala et al., 2021 source
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- Premisecitation
Brain-wide complete reconstruction of single neuron morphology is currently the only method to capture the full extent of a neuron's axon projection pattern and define projection neuron types.
“Brain-wide complete reconstruction of single neuron morphology is currently the only approach to capture the full extent of a neuron’s axon projection pattern and define projection neuron types (Gao et al., 2022; Peng et al., 2021; Winnubst et al., 2019).”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
In each mouse motor cortex subclass, morpho-electrical properties change continuously together with transcriptomic types.
“Within each subclass the morpho-electrical properties vary continuously along with the transcriptomic types.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Scala et al., 2021 source
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- Interpretationreasoning
Because spatial distribution patterns are defined during development, transcriptomes may retain the developmental plan.
“Since the spatial distribution pattern is defined during development, this suggests that transcriptomes may retain the developmental plan.”
Quote in the paperSubstantial claim - Premisecitation
Transcriptomically derived taxonomies in adult mammalian brain consistently show a hierarchical organization of cell types.
“Transcriptomically derived cell type taxonomies in the adult mammalian brain, with majority of the studies conducted in mouse, have consistently revealed a hierarchical organization of cell types (Fig. 2) (Brain Initiative Cell Census Network, 2021; Macosko et al., 2015; Romanov et al., 2017; Russ et al., 2021; Saunders et al., 2018; Shekhar et al., 2016; Tasic et al., 2016; Tasic et al., 2018;”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisenone given
Most phenotypic measurements, including single-cell transcriptome, are only a one-time snapshot of the cell.
“This is a difficult question since most of the phenotypic measurements including the single-cell transcriptome are only a one-time snapshot of the cell.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Transcriptomic and epigenomic classification is a good proxy for cell type classification because regulatory mechanisms for cell identity are embedded in these data.
“Like phylogenomics for species classification, transcriptomic (and epigenomic) classification is a good proxy of cell type classification as the gene regulatory mechanisms that encode and maintain cell type identities are embedded in the transcriptomes and epigenomes.”
Quote in the paperSubstantial claim - Interpretationcitation
Continuous variations among cortical neuron types in transcriptomic space correspond strongly to their continuous spatial distribution along cortical depth.
“Thus, a strong correspondence is demonstrated here between the continuous variations among cortical neuron types in the transcriptomic space and their continuous and directed spatial distribution patterns.”
Quote in the paperSubstantial claim - Premisecitation
Specific sets of cell adhesion molecules provide guidance cues for axon path finding and synapse formation, leading to assembly of region- and cell type-specific local and global circuit networks.
“Third, specific sets of cell adhesion molecules provide guidance cues for axon path finding and synapse formation, leading to the assembly of region- and cell type-specific local and global circuit networks.”
Quote in the paperNot a substantial claim0 of 3 sources checked - Interpretationreasoning
Taken together, non-neuronal cell types actively respond to and contribute to different physiological and pathological changes in the brain.
“Taken together, these studies paint a collective picture on how the variety of non-neuronal cell types actively respond to and contribute to different physiological and pathological changes in the brain.”
Quote in the paperSubstantial claim - Premisecitation
Driven by transcription factor networks, each type of neural progenitor generates a series of neuronal cell types.
“Second, driven by the transcription factor network, each type of neural progenitors generates a series of neuronal cell types.”
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There are transient cell types and circuits that mainly exist during development and have developmental stage-specific functions.
“Finally, there are transient cell types and circuits that mainly exist during development and have developmental stage-specific functions (Cossart and Garel, 2022; Molnar et al., 2020).”
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- cites Molnar et al., 2020 source
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- Interpretationcitation
Many non-neuronal cell types in the brain, despite lower diversity than neurons in baseline adult state, undergo pronounced changes and exhibit many different cell states under different physiological or diseased conditions.
“Here I highlight a prominent feature of the non-neuronal cell types in the brain, which is that despite having lower diversity than neurons in baseline adult state, many non-neuronal cell types undergo pronounced changes, i.e., they exhibit many different cell states, under different physiological or diseased conditions.”
Quote in the paperSubstantial claim - Interpretationreasoning
Cell type development is not a simple linear process but a highly multifaceted process leading to a complex cell type landscape that underlies the richness of cell type function.
“All these observations, and more to be discovered, contribute to a nuanced understanding that cell type development is not a simple linear process, but a highly multifaceted process leading to the complex cell type landscape described in the above sections, which underlies the richness of cell type function.”
Quote in the paperSubstantial claim - Premisecitation
The development of a cell type may not follow a simple trajectory but involves multiple steps of divergent or convergent differentiation.
“The development of a cell type may not follow a simple trajectory but involves multiple steps of divergent or convergent differentiation (Shekhar et al., 2022), the former due to the multipotency of progenitors or transitional cell types and the latter due to convergence of different transitional types.”
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InterpretationreasoningSingle-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 claimMay combine two claims.
PremisecitationGlutamatergic 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- cites Tasic et al., 2018 source
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Interpretationnone givenWhether 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.”
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InterpretationreasoningA 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).
InterpretationreasoningSome 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 claimProbably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningSpecific 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 claimProbably not a substantial claim: may not pass S4 (based). May combine two claims.
Interpretationnone givenCell 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 claimProbably not a substantial claim: may not pass S4 (based). May combine two claims.
Premisenone givenTranscriptomic 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 claimMay combine two claims.
PremisecitationA 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).”
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PremisecitationTo 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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PremisecitationCells 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).”
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PremisecitationOligodendrocyte 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).”
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PremisecitationDevelopmental 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”
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- cites Sagner and Briscoe, 2019
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- cites Sulston et al., 1983 source
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Premisenone givenThe 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 claimProbably not a substantial claim: may not pass S2 (checkable), S4 (based). May combine two claims.
Interpretationnone givenCell 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 claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Interpretationnone givenIndividual 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 claimMay combine two claims.
PremisecitationMicroglia 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 checkedClassified as probably not a substantial claim.
Premisenone givenThe 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 claimMay combine two claims.
PremisecitationOpposing 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.”
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PremisecitationExtensive 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).”
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PremisecitationMyelination exhibits activity-dependent plasticity.
“Myelination process also exhibits activity-dependent plasticity (Monje, 2018).”
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PremisereasoningThe 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 claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAstrocytes 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).”
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- cites Khakh and Deneen, 2019
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PremisecitationThe 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”.”
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PremisecitationLater 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.”
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PremisecitationSingle-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).”
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PremisecitationReactive 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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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”
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 measuredSingle-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.”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [2]
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).”
From A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain (2023) · cites this paper as [2]
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A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
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Self-citationEvolution of neuronal cell classes and types in the vertebrate retina
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“Advances in high-throughput single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have enabled related activity focused on determining the extent to which cell types, the functional units of complex tissues 6,7 , are conserved among species.”
A Review of Single-Cell RNA-Seq Annotation, Integration, and Cell–Cell Communication
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“Defining a cell type is not a trivial question [41].”
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Hippocampal GABAergic interneurons and memory
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“Developing a brain cell-type taxonomy requires integrating various molecular modalities, verifying cell clusters on the basis of multiple molecular information and applying a uniform nomenclature 29 .”
Self-citationPurification and characterization of human neural stem and progenitor cells
Liu, D. D., He, J. Q., Sinha, R., Eastman, A. E., Toland, A. M. S., Morri, M., Neff, N. F., Vogel, H. S., Uchida, N., & Weissman, I. L. (2023) · Cell · doi:10.1016/j.cell.2023.02.017 · Cited by 124 · see citing works
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Self-citationCancer cell states: Lessons from ten years of single-cell RNA-sequencing of human tumors
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Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution
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A reference cell tree will serve science better than a reference cell atlas
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Benchmarking strategies for cross-species integration of single-cell RNA sequencing data
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Neuroscience Needs Network Science
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“Single-cell transcriptomics has also enabled rapid and diverse profiling of cellular identity in various animals, developmental stages, and brain health patterns (Zeng, 2022).”
BackgroundSelf-citationBravo González-Blas, C., Matetovici, I., Hillen, H., Taskiran, I. I., Vandepoel, R., Christiaens, V., Sansores-García, L., Verboven, E., Hulselmans, G., Poovathingal, S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-023-01316-4 · Cited by 85 · see citing works
“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 microenvironment 4 .”
The future of rapid and automated single-cell data analysis using reference mapping
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Schneider-Mizell, C. M., Bodor, Á. L., Brittain, D., Buchanan, J., Bumbarger, D. J., Elabbady, L., Gamlin, C. R., Kapner, D., Kinn, S., Mahalingam, G., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.23.525290 · Cited by 70 · see citing works
Molecular taxonomy of nociceptors and pruriceptors
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Inhibitory specificity from a connectomic census of mouse visual cortex
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“Cell types are identified based on many factors including their function, morphology, developmental origin, and regional context ( 36 – 38 ).”
BackgroundVirtual Fly Brain—An interactive atlas of the Drosophila nervous system
Court, R., Costa, M., Pilgrim, C., Millburn, G., Holmes, A., McLachlan, A. D., Larkin, A., Matentzoglu, N., Kır, H., Parkinson, H., et al. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1076533 · Cited by 51 · see citing works
“The concept of cell type is even more controversial (Bates et al., 2019; Zeng, 2022), but neurobiologists typically group cells sharing morphological, connectomic, functional and developmental properties together under a common name, and generally refer to such groupings as types.”
BackgroundAdvances and applications in single-cell and spatial genomics
Wang, J., Ye, F., Chai, H., Jiang, Y., Wang, T., Ran, X., Xia, Q., Xu, Z., Fu, Y., Zhang, G., et al. (2024) · Science China Life Sciences · doi:10.1007/s11427-024-2770-x · Cited by 69 · see citing works
A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types
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“1,3,11,83 We utilized single-cell transcriptomic and epigenomic data to identify marker genes for the generation of transgenic lines, as well as putative enhancers for the creation of enhancer AAVs, and evaluated their specificity for experimental access to cortical cell types.”
Mapping visual functions onto molecular cell types in the mouse superior colliculus
Liu, Y., Savier, E. L., DePiero, V. J., Chen, C., Schwalbe, D. C., Abraham‐Fan, R., Chen, H., Campbell, J. N., & Cang, J. (2023) · Neuron · doi:10.1016/j.neuron.2023.03.036 · Cited by 59 · see citing works
“These studies have generated rich information regarding neuronal diversity and identified genetic access points to specific neuronal populations for mechanistic investigations.(1) However, even though the connection between morphology and function has been firmly established, the link between functional and molecular…”
A guide to the BRAIN Initiative Cell Census Network data ecosystem
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Self-citationThe cell-type underpinnings of the human functional cortical connectome
Zhang, X.-H., Anderson, K. M., Dong, H.-M., Chopra, S., Dhamala, E., Emani, P. S., Gerstein, M., Margulies, D. S., & Holmes, A. J. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01812-2 · Cited by 62 · see citing works
“Although these multidimensional features do not necessarily vary concurrently, recent developments in high-throughput single-nucleus RNA-sequencing (snRNA-seq) data have played a key role in characterizing broad profiles of cellular gene expression 34 .”
Voyager: exploratory single-cell genomics data analysis with geospatial statisticsPreprint
Moses, L., Einarsson, P. H., Jackson, K. C., Luebbert, L., Booeshaghi, A. S., Antonsson, S. E., Bray, N., Melsted, P., & Pachter, L. S. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.20.549945 · Cited by 57 · see citing works
“However, with more considerations on the nature of cell types 72,73 and ESDA of categorical variables, categorical methods may be added in future versions.”
Causal evidence of a line attractor encoding an affective state
Vinograd, A., Nair, A., Kim, J. H., Linderman, S. W., & Anderson, D. J. (2024) · Nature · doi:10.1038/s41586-024-07915-x · Cited by 63 · see citing works
“One focuses on understanding behaviourally specialized neuron types and their functional connectivity 8–10 , whereas the other investigates emergent properties of neural networks, such as attractors 1,3,11 .”
Methods and Insights from Single-Cell Expression Quantitative Trait Loci
Kang, J. B., Raveane, A., Nathan, A., Soranzo, N., & Raychaudhuri, S. (2023) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-101422-100437 · Cited by 53 · see citing works
“While the concept of cell types is nuanced (168), they can be thought of as biologically functional units playing distinct roles—for example, the pancreas contains hormone-producing types, like alpha and beta cells, as well as supporting cell types, like endothelial cells and fibroblasts.”
BackgroundFourth Report on Chicken Genes and Chromosomes 2022
Smith, J., Alfieri, J. M., Anthony, N., Arensburger, P., Athrey, G., Balacco, J., Balic, A., Bardou, P., Barela, P., Bigot, Y., et al. (2022) · Cytogenetic and Genome Research · doi:10.1159/000529376 · Cited by 52 · see citing works
Transcriptomic neuron types vary topographically in function and morphology
Shainer, I., Kappel, J. M., Laurell, E., Donovan, J. C., Schneider, M., Kuehn, E., Arnold-Ammer, I., Stemmer, M., Larsch, J., & Baier, H. (2025) · Nature · doi:10.1038/s41586-024-08518-2 · Cited by 54 · see citing works
A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons
Winter, C. C., Jacobi, A., Su, J., Chung, L., van Velthoven, C. T. J., Yao, Z., Lee, C., Zhang, Z., Yu, S., Gao, K., et al. (2023) · Nature · doi:10.1038/s41586-023-06817-8 · Cited by 42 · see citing works
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“Conversely, control samples needed to be classified by (1) CERAD protocol as “no AD” or “possible AD” and (2) Braak AD staging protocol within the stage 0-2.”
Ning, K., Lu, B., Wang, X., Zhang, X., Nie, S., Jiang, T., Li, A., Fan, G., Wang, X., Luo, Q., et al. (2023) · Light Science & Applications · doi:10.1038/s41377-023-01230-2 · Cited by 48 · see citing works
The heterocellular heart: identities, interactions, and implications for cardiology
Lother, A., & Kohl, P. K. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01000-6 · Cited by 43 · see citing works
“The rise of single-cell RNA-seq (scRNA-seq) technologies and the accompanying possibility of making ever more subtle distinctions, but also the user-dependence of RNA-seq data analysis, presentation and interpretation, have refuelled the ongoing debate on how to define a ‘cell type’ [123, 195, 218].”
BackgroundThe cell type composition of the adult mouse brain revealed by single cell and spatial genomicsPreprint
Langlieb, J., Sachdev, N., Balderrama, K. S., Nadaf, N. M., Raj, M., Murray, E. M., Webber, J. T., Vanderburg, C. R., Gazestani, V., Tward, D. J., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.06.531307 · Cited by 44 · see citing works
“Although the precise number of distinct cell types present in the brain is unknown, the number is presumed to be in the thousands 1,2 .”
BackgroundInterneuron diversity in the human dorsal striatum
Garma, L. D., Harder, L., Barba-Reyes, J. M., Salas, S. M., Díez-Salguero, M., Nilsson, M. F., Serrano‐Pozo, A., Hyman, B. T., & Muñoz‐Manchado, A. B. (2024) · Nature Communications · doi:10.1038/s41467-024-50414-w · Cited by 48 · see citing works
Mapping the topography of spatial gene expression with interpretable deep learning
Chitra, U., Arnold, B. J., Sarkar, H., Sanno, K., Ma, C., Lopez-Darwin, S. L., & Raphael, B. J. (2025) · Nature Methods · doi:10.1038/s41592-024-02503-3 · Cited by 63 · see citing works
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Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex
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The brain is not mental! coupling neuronal and immune cellular processing in human organisms
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“Studies going back to Ramon y Cajal revealed that cell types in the brain and body display several properties in many modalities (e.g., molecular, morphological, physiological, and functional) (Zeng and Sanes, 2017; see Zeng, 2022 for a recent review).”
BackgroundPredictive and robust gene selection for spatial transcriptomics
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Spotiphy enables single-cell spatial whole transcriptomics across an entire section
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Single-cell multi-omics and lineage tracing to dissect cell fate decision-making
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“The blueprint that underlies the development of a human body, consisting of over 30 trillion cells and organized into a myriad of organ systems each composed of diverse cell types and states, is orchestrated by information encoded in our genomes (Zeng, 2022).”
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“We must also embrace the fact that a consensus definition of a cell type is currently lacking 40 , but even if the question of the absolute number of cell types in the brain cannot be fully addressed, we can be successful in defining their transcriptomic marker genes.”
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Self-citationIntrinsic neural diversity quenches the dynamic volatility of neural networks
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Multimodal cortical neuronal cell type classification
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“This approach enables the identification of previously unknown cell types, revealing their unique genetic signatures and paving the way for a more comprehensive and nuanced classification of cortical neuronal cell types [40, 41].”
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Continuous cell-type diversification in mouse visual cortex development
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“…intersectional genetic strategies, and expansion of the toolset to tag populations based on dynamic cellular processes, the decade of neuroscience research will see remarkable advances in the parsing of these important cells into increasingly refined sub-classes (Bugeon et al., 2022; Zeng, 2022).”
BackgroundA multi-tissue single-cell expression atlas in cattle
Han, B., Li, H., Zheng, W., Zhang, Q., Chen, A., Zhu, S., Shi, T., Wang, F., Zou, D., Yu, S., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02329-5 · Cited by 36 · see citing works
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Molecular and functional diversity of the autonomic nervous system
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“The subsequent maturation of molecular and genetic tools allowed different neuron classes to be further defined 136–139 .”
The Central Extended Amygdala Guides Survival-Relevant Tradeoffs for Action SelectionPreprint
Holley, D., & Fox, A. S. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104879 · Cited by 23 · see citing works
“It is also possible, however, that this appearance of multifunctionality could arise as a product of within-cell-type heterogeneity, and that intermingled groups of ostensibly specific EAc neurons might be further functionally dissociable (e.g., see Zeng, 2022).”
BackgroundA dynamic and multimodal framework to define microglial states
Sankowski, R., & Prinz, M. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01978-3 · Cited by 29 · see citing works
Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocks
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“This approach allowed us to examine further the morphological diversity of several major subclasses of GABAergic neurons 65 , classified by their transcriptomic profiles, within the mouse cerebral cortex.”
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“50 This type of question could be explored through the access of sequential samples of CHB patients using fine-needle aspirates, 51 52 and the use of in vivo and ex vivo models for the characterisation of inflammatory responses.”
BackgroundEmbryonic temporal-spatial delineation of excitatory spinal V3 interneuron diversity
Deska‐Gauthier, D., Borowska-Fielding, J., Jones, C., Zhang, H., Mackay, C., Michail, R., Bennett, L. A., Bikoff, J. B., & Zhang, Y. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113635 · Cited by 21 · see citing works
Cellular and Synaptic Diversity of Layer 2-3 Pyramidal Neurons in Human IndividualsPreprint
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scELMo: Embeddings from Language Models are Good Learners for Single-cell Data Analysis
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“Cell-type annotation is a foundational problem in the single-cell analysis [41].”
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“Given the complexity of brain circuits, neuronal subtypes must be characterized from multiple view-points ( Zeng, 2022 ).”
BackgroundGenetically defined neuron types underlying visuomotor transformation in the superior colliculus
Cang, J., Chen, C., Li, C., & Liu, Y. (2024) · Nature reviews. Neuroscience · doi:10.1038/s41583-024-00856-4 · Cited by 22 · see citing works
Dissecting the cellular architecture and genetic circuitry of the soybean seed
Pelletier, J. M., Chen, M., Lin, J.-Y., Le, B. H., Kirkbride, R. C., Hur, J., Wang, T., Chang, S.-H., Olson, A., Nikolov, L. A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2416987121 · Cited by 26 · see citing works
A standardized nomenclature for the rods and cones of the vertebrate retina
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“Rods (PR0) are omitted for simplicity.”
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“Encompassing neurons and glia, these cells can be categorized into a large number of different types—based upon developmental, anatomical, molecular, and functional properties [1,2]—with diverse roles.”
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A suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell typesPreprint
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“The definition of cell types and their taxonomy in the central nervous system and genetic access to each one are essential for our understanding of how they contribute to nervous system function and dysfunction 2,58,59 .”
Scalable spatial single-cell transcriptomics and translatomics in 3D thick tissue blocksPreprint
Sui, X., Lo, J. A., Luo, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.08.05.606553 · Cited by 23 · see citing works
“In this study, we also elucidate the morphological diversity of several major subclasses of GABAergic neurons 64 , classified by their transcriptomic profiles, within the mouse cerebral cortex.”
BackgroundGene panel selection for targeted spatial transcriptomics
Zhang, Y., Petukhov, V., Biederstedt, E., Que, R. A., Zhang, K., & Kharchenko, P. V. (2024) · Genome biology · doi:10.1186/s13059-024-03174-1 · Cited by 21 · see citing works
Single-cell DNA Methylome and 3D Multi-omic Atlas of the Adult Mouse BrainPreprint
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Regulation of alternative splicing and polyadenylation in neurons
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“Although all researchers can debate what the most interesting cell types are, it is without question that neurons comprise one of the most diverse subclasses of cell types (Zeng, 2022).”
BackgroundEnriched Single-Nucleus RNA-Sequencing Reveals Unique Attributes of Distal Convoluted Tubule Cells
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Chinese Immune Multi-Omics Atlas
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A roadmap for delivering a human musculoskeletal cell atlas
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“This variability complicates efforts in developing a cell atlas, and it is important to capture, annotate and categorize the information that defines a particular cell type (or state) to enable the generation of tractable, suitably resolved cellular maps 9 .”
BackgroundThe energetics of cellular life transitions
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“A cell’s hardware includes the proteins encoded by the sequences of its genome that are epigenetically “open” and active or “closed” and repressed, plus the complex set of organelles, proteins, and molecules it contains at any given time [19].”
Multimodal classification of neurons in the lateral septumPreprint
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Molecular gradients shape synaptic specificity of a visuomotor transformation
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Biophysically interpretable inference of cell types from multimodal sequencing data
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“The definition of type, and whether designations should be discrete or continuous, is a matter of debate 10,11 (and often investigation-dependent).”
Hu, H., & Quon, G. (2024) · Nature Communications · doi:10.1038/s41467-024-53971-2 · Cited by 18 · see citing works
Implementation and validation of single-cell genomics experiments in neuroscience
Colonna, M., Konopka, G., Liddelow, S. A., Nowakowski, T. J., Awatramani, R. B., Bateup, H. S., Cadwell, C. R., Caglayan, E., Chen, J. L., Gillis, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01814-0 · Cited by 22 · see citing works
“While the definition of a cell type typically invokes other features (e.g., connectivity, function, and morphology), these features can be difficult or impossible to acquire in many species or in high throughput 15,96 .”
In Situ Synthesis and Assembly of Functional Materials and Devices in Living Systems
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Identifying neuron types and circuit mechanisms in the auditory midbrain
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- Authors
- Zeng, H.
- Affiliations
- Allen Institute for Brain Science (US)
- Corresponding author
- Zeng, Hongkui
- ORCID
- Zeng, Hongkui
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-07
- Volume
- 185
- Issue
- 15
- Pages
- 2739-2755
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC9342916
- OpenAlex
- W4286449197
- Semantic Scholar
- fcb96c79ea7a1b1e583da762c3405f5296bcb8d6
- 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
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 385 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- 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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