Cited by 1,065Single-cell and spatial transcriptomicsNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index; none of the 65 sources its claims cite is checked for support yet.

A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Open access

Published version of a preprint

Abstract

SUMMARY The isocortex and hippocampal formation (HPF) in the mammalian brain play critical roles in perception, cognition, emotion and learning. We profiled ~1.3 million cells covering the entire adult mouse isocortex and HPF and derived a transcriptomic cell type taxonomy revealing a comprehensive repertoire of glutamatergic and GABAergic neuron types. Contrary to the traditional view of HPF as having a simpler cellular organization, we discover a complete set of glutamatergic types in HPF homologous to all major subclasses found in the six-layered isocortex, suggesting that HPF and isocortex share a common circuit organization. We also identify large-scale continuous and graded variation of cell types along isocortical depth, across isocortical sheet and in multiple dimensions in hippocampus and subiculum. Overall, our study establishes a molecular architecture of mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity and function of these brain structures.

Overview

Integrity signals

Registry

Crossref · 10.1016/j.cell.2021.04.021

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 65 cited sources checked · 0 supported · 0 flagged

  • It may state two separate claims as one. 123
  • Probably not a substantial claim. 43
  • The quote only partly states this claim. 1
142 of 142
  • The authors state this as an assumption.

    A systematic study is needed for a complete picture of the number and distribution of cell types in isocortex and HPF and for understanding how these regions interact with the rest of the brain.

    “But a systematic study is needed for a complete picture of the number and distribution of cell types in these regions and for understanding how different cortical and hippocampal regions interact with the rest of the brain and carry out their individual functions.”
  • The paper relies on this without support.

    Fewer differentially expressed genes between two clusters indicates greater relatedness or similarity.

    “the fewer DE genes, the more related”
  • The paper relies on this without support.

    Correlation of gene expression between HPF and CTX clusters indicates homology.

    “correlating gene expression for each HPF cell to the average expression of each CTX cluster”
  • The paper relies on this without support.

    Mouse isocortex and hippocampal formation are representative of mammalian isocortex and hippocampal formation.

    “our study establishes a molecular architecture of mammalian isocortex and hippocampal formation”
  • The paper relies on this without support.

    Transcriptomic neighborhoods of GABAergic neurons correlate with distinct developmental origins (CGE and MGE).

    “The GABAergic inhibitory neuronal class is divided into two neighborhoods that correlate with distinct developmental origins: caudal ganglionic eminence (CGE) (Fig. 2A–E) and medial ganglionic eminence (MGE) (Fig. 2F–J).”
  • The paper relies on this without support.

    The anatomical locations assigned using existing RNA ISH data from the Allen Mouse Brain Atlas and a limited Visium dataset are accurate enough for major cell types.

    “we assigned anatomical locations of major cell types (mostly at the supertype level) using existing RNA ISH data from the Allen Mouse Brain Atlas and a limited Visium dataset”
  • The paper relies on this without support.

    The relative proportions estimated from 10xv2 data reflect true proportions of cell types in each region.

    “we also provided an estimate of the relative proportions of different cell types in each region using the 10xv2 data”
  • The paper relies on this without support.

    The top principal component computed from a selected gene set faithfully represents the biological axis it is named after (e.g., Pr-Di, Do-Ve, Su-De, activity).

    “The top PC based on this set of genes is defined as the CA3 Pr-Di axis”
    “defined the pseudo superficial-deep (Su-De) axis as the top PC based on these layer-specific genes”
    “computed the top PC based on this gene set as the activity axis”
  • The paper relies on this without support.

    The 10xv2 and SSv4 datasets share conserved global transcriptional signatures that permit cross-platform mapping of regional identity.

    “the prediction was based on global transcription signatures that are conserved across platforms”
  • The paper relies on this without support.

    Donor-specific transcriptional signatures are subtle and do not affect the global clustering results.

    “While donor-specific transcriptional signatures are subtle and do not affect the global clustering results”
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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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Class-level subclass counts omit two subclasses

    Minor

    The four class counts of 6, 28, 2, and 4 subclasses sum to 40 rather than 42. CR and Meis2 are subsequently identified as neuronal subclasses, but are not accounted for in the stated class breakdown.

    Reported 42 · recomputed 40

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Metadata

Authors
Yao, Z., van Velthoven, C. T. J., Nguyen, T. N., Goldy, J., Sedeno-Cortes, A. E., Baftizadeh, F., Bertagnolli, D., Casper, T., Chiang, M., Crichton, K., Ding, S.-L., Fong, O., Garren, E., Glandon, A., Gouwens, N. W., Gray, J., Graybuck, L. T., Hawrylycz, M. J., Hirschstein, D., Kroll, M., Lathia, K., Lee, C., Levi, B., McMillen, D., Mok, S., Pham, T., Ren, Q., Rimorin, C., Shapovalova, N., Sulc, J., Sunkin, S. M., Tieu, M., Torkelson, A., Tung, H., Ward, K., Dee, N., Smith, K. A., Tasic, B., & Zeng, H.
Affiliations
Allen Institute for Brain Science (US)
Corresponding author
Zeng, Hongkui
Venue
Cell
Publisher
Elsevier BV
Published
2021-06
Volume
184
Issue
12
Pages
3222-3241.e26
ISSN
0092-8674 (ISSN-L)
OpenAlex
W3162218953
Cited by
1,065
References
85
Citations by year
2026: 189 · 2025: 223 · 2024: 243 · 2023: 186 · 2022: 122 · 2021: 83
FWCI
50.70
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
neocortex, hippocampal formation, glutamatergic neurons, GABAergic neurons, neuronal cell types, subiculum, mouse brain, single-cell transcriptomics
MeSH terms
Animals, Hippocampus, Mice, Inbred C57BL, Mice, Transgenic, Glutamic Acid, Neocortex, Mice, GABAergic Neurons, Transcriptome

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