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Conserved cell types with divergent features in human versus mouse cortex
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Abstract
Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.
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“As a third example of the great elaboration and specialization associated with consciousness, the more-advanced animal brains have the largest numbers of neuron types, with highly complex interactions (Strausfeld, 2012; Feinberg and Mallatt, 2016a; Hodge et al., 2019).”
From Phenomenal Consciousness and Emergence: Eliminating the Explanatory Gap (2020) · cites this paper as Hodge et al., 2019
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Single-cell RNA-sequencing (scRNA-seq) studies have systematically characterized and classified cell types in individual regions of isocortex and hippocampus”
From A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2021) · cites this paper as Hodge et al., 2019
The cited source says what the claim attributes to it.
In the citing paper
“nuclei were sorted using a standard gating strategy to exclude multiplets24”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [24]
In the citing paper
“8 out of 14 modules showed greater intra-module correlation than a comparable random gene set in the adult human brain dataset from Hodge et al (30) (Fig. 4B).”
From In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes (2020) · cites this paper as [30]
In the citing paper
“In addition, multiplex FISH is already being used to measure the proportions of transcriptomic types within a given brain tissue (Hodge et al., 2019; Moffitt et al., 2018; Zhang et al., 2020).”
From Integrated Morphoelectric and Transcriptomic Classification of Cortical GABAergic Cells (2020) · cites this paper as Hodge et al., 2019
In the citing paper
“The application of single-cell RNA sequencing (scRNA-seq) to the neocortex and other brain regions has revealed a complex but tractable hierarchical organization of transcriptomic cell types that are consistent overall with knowledge from decades of anatomical, physiological and developmental studies but with an unmatched level of granularity7–11.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [10]
In the citing paper
“Substantiating previous studies9,10, our multimodal cross-species study of the primary motor cortex suggests that a general principle of cortical cell-type organization is its hierarchical relationship, whereby high-level classes linked by major branches comprise progressively finer subpopulations connected by minor branches.”
From A multimodal cell census and atlas of the mammalian primary motor cortex (2021) · cites this paper as [10]
In the citing paper
“Comparing human with mouse and non-human primates reveals both conserved and distinct cell type signatures, including species-specific differences in the proportions of cell populations and in gene expression within homologous cell classes and types (Bakken et al., 2020; Hodge et al., 2019; Krienen et al., 2020).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Hodge et al., 2019
In the citing paper
“Evolutionary conservation and divergence provide insight into the gene regulatory programs that were selected for their impact on cognitive function (Bakken et al., 2020; Hodge et al., 2019; Krienen et al., 2020).”
From Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes (2021) · cites this paper as Hodge et al., 2019
In the citing paper
“We observed numerous genes with categorical changes in cell-type-specific expression patterns (including NTNG1, IQGAP2 and TRPC3) and, in rare cases, genes that were a specific marker in one cell class in some species but not detected at all in the interneurons of the other species11”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [11]
In the citing paper
“which suggests that the genes that encode these markers stably delineate a core repertoire of neocortical interneuron types in these species11,15,18”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [11]
In the citing paper
“The expansion of this LAMP5+ LHX6+ cell type throughout the neocortex in diverse primates probably explains a recent observation11 that this cell type is much more abundant in the human temporal lobe than in the mouse V1.”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [11]
In the citing paper
“they obtained 45 human interneuron clusters, whereas our marmoset data resolved to 22 clusters”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [11]
In the citing paper
“However, in agreement with other reports11, these types were inconsistently observed across individual animals and regions, likely due to laminar location and low abundance, and were not analysed further.”
From Innovations present in the primate interneuron repertoire (2020) · cites this paper as [11]
In the citing paper
“Notably, this approach provides the means to evaluate and compare the circuit contributions and function of PV cINs across species, regardless of their genetic accessibility44,45.”
From Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans (2020) · cites this paper as [44]
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InfluentialCOVID-19 and the Chemical Senses: Supporting Players Take Center Stage
Cooper, K. W., Brann, D. H., Farruggia, M. C., Bhutani, S., Pellegrino, R., Tsukahara, T., Weinreb, C., Joseph, P. V., Larson, E. D., Parma, V., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.032 · Cited by 341
Single-Nucleus RNA-Seq Is Not Suitable for Detection of Microglial Activation Genes in Humans
Thrupp, N., Sala Frigerio, C., Wolfs, L., Skene, N. G., Fattorelli, N., Poovathingal, S., Fourne, Y., Matthews, P. M., Theys, T., Mancuso, R., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108189 · Cited by 329
“, 2017), Allen Institute for Brain Science (AIBS) (Hodge et al., 2019), Tasic (Tasic et al.”
BackgroundA single-cell atlas of the normal and malformed human brain vasculature
Winkler, E. A., Kim, C. N., Ross, J. M., Garcia, J. H., Gil, E., Oh, I., Chen, L. Q., Wu, D., Catapano, J. S., Raygor, K. P., et al. (2022) · Science · doi:10.1126/science.abi7377 · Cited by 324
“Because of biases in cell isolation, existing human brain cell atlas studies have overlooked the cerebrovasculature, and its cellular heterogeneity has been largely unexplored in humans (15, 16).”
In vivo Perturb-Seq reveals neuronal and glial abnormalities associated with autism risk genes
Jin, X., Simmons, S. K., Guo, A., Shetty, A. S., Ko, M., Nguyen, L., Jokhi, V., Robinson, E., Oyler, P., Curry, N., et al. (2020) · Science · doi:10.1126/science.aaz6063 · Cited by 317
“Cell type Adult human brain (Hodge et al 2019) (29)”
BackgroundFranjic, D., Skarica, M., Ma, S., Arellano, J. I., Tebbenkamp, A. T. N., Choi, J., Xu, C., Li, Q., Morozov, Y. M., Andrijevic, D., et al. (2022) · Neuron · doi:10.1016/j.neuron.2021.10.036 · Cited by 308
“InN clusters were first classified to major groups based on the expression of three canonical function markers (PVALB, SST, VIP) as well as LAMP5, a marker mostly representing a group of neurogliaform InN and recently being adopted as a major InN marker (Tasic et al., 2018; Hodge et al., 2019).”
InfluentialMolecular landscapes of human hippocampal immature neurons across lifespan
Zhou, Y. F., Su, Y., Li, S., Kennedy, B. C., Zhang, D. Y., Bond, A. M., Sun, Y. Y., Jacob, F., Lu, L., Hu, P., et al. (2022) · Nature · doi:10.1038/s41586-022-04912-w · Cited by 314
Gyllborg, D., Langseth, C. M., Qian, X., Choi, E., Salas, S. M., Hilscher, M. M., Lein, E. S., & Nilsson, M. F. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa792 · Cited by 308
Self-citationHuman cerebral organoids — a new tool for clinical neurology research
Eichmüller, O. L., & Knoblich, J. A. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00723-9 · Cited by 319
Molecular atlas of the adult mouse brain
Ortiz, C., Navarro, J. F., Jurek, A., Märtin, A., Lundeberg, J., & Meletis, K. (2020) · Science Advances · doi:10.1126/sciadv.abb3446 · Cited by 286
Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials
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Large-scale neural recordings with single neuron resolution using Neuropixels probes in human cortex
Paulk, A. C., Kfir, Y., Khanna, A. R., Mustroph, M. L., Trautmann, E. M., Soper, D. J., Stavisky, S. D., Welkenhuysen, M., Dutta, B., Shenoy, K. V., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-00997-0 · Cited by 283
Identification of neural oscillations and epileptiform changes in human brain organoids
Samarasinghe, R. A., Miranda, O. A., Buth, J. E., Mitchell, S. A., Ferando, I., Watanabe, M., Allison, T. F., Kurdian, A., Fotion, N. N., Gandal, M. J., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00906-5 · Cited by 288
Human neocortical expansion involves glutamatergic neuron diversification
Berg, J., Sorensen, S. A., Ting, J. T., Miller, J. A., Chartrand, T., Buchin, A., Bakken, T. E., Budzillo, A., Dee, N., Ding, S.-L., et al. (2021) · Nature · doi:10.1038/s41586-021-03813-8 · Cited by 285
Self-citationA connectomic study of a petascale fragment of human cerebral cortex
Shapson-Coe, A., Januszewski, M., Berger, D. R., Pope, A., Wu, Y., Blakely, T., Schalek, R. L., Li, P. H., Wang, S., Maitin-Shepard, J., et al. (2021) · doi:10.1101/2021.05.29.446289 · Cited by 243
“The input FoV was [403,403,42] voxels centered around the example points, corresponding to an output size of [191,191,14].”
BackgroundSingle-cell epigenomics reveals mechanisms of human cortical development
Ziffra, R. S., Kim, C. N., Ross, J. M., Wilfert, A. B., Turner, T. N., Haeussler, M., Casella, A. M., Przytycki, P. F., Keough, K. C., Shin, D. S., et al. (2021) · Nature · doi:10.1038/s41586-021-03209-8 · Cited by 272
DNA methylation atlas of the mouse brain at single-cell resolution
Liu, H., Zhou, J., Tian, W., Luo, C., Bartlett, A., Aldridge, A., Lucero, J., Osteen, J. K., Nery, J. R., Chen, H., et al. (2021) · Nature · doi:10.1038/s41586-020-03182-8 · Cited by 289
Macroscopic gradients of synaptic excitation and inhibition in the neocortex
Wang, X. (2020) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-0262-x · Cited by 289
Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH
Fang, R., Xia, C., Close, J. L., Zhang, M., He, J., Huang, Z., Halpern, A. R., Long, B., Miller, J. A., Lein, E. S., et al. (2022) · Science · doi:10.1126/science.abm1741 · Cited by 277
“Combining scRNA-seq with microdissection (8), and more recently in situ sequencing targeting 120 genes (9), have revealed the laminar organization of these transcriptionally defined neuronal cell types, in particular the excitatory neurons, in the human MTG.”
BackgroundMethodInfluentialSelf-citationBroad transcriptomic dysregulation occurs across the cerebral cortex in ASD
Gandal, M. J., Haney, J. R., Wamsley, B., Yap, C. X., Parhami, S., Emani, P. S., Chang, N., Chen, G. T., Hoftman, G. D., de Alba, D., et al. (2022) · Nature · doi:10.1038/s41586-022-05377-7 · Cited by 283
Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans
Vormstein-Schneider, D., Lin, J. D., Pelkey, K. A., Chittajallu, R., Guo, B., Arias-Garcia, M. A., Allaway, K., Sakopoulos, S., Schneider, G., Stevenson, O., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0692-9 · Cited by 235
Single-Cell Sequencing of Brain Cell Transcriptomes and Epigenomes
Armand, E. J., Li, J., Xie, F., Luo, C., & Mukamel, E. A. (2021) · Neuron · doi:10.1016/j.neuron.2020.12.010 · Cited by 241
“Comparing human with mouse and non-human primates reveals both conserved and distinct cell type signatures, including species-specific changes in the proportion of cell populations and in gene expression within homologous cell classes and types (Bakken et al., 2020; Hodge et al., 2019; Krienen et al., 2020) .”
BackgroundMolecular signatures underlying neurofibrillary tangle susceptibility in Alzheimer’s disease
Otero-Garcia, M., Mahajani, S. U., Wakhloo, D., Tang, W., Xue, Y.-Q., Morabito, S., Pan, J., Oberhauser, J., Madira, A. E., Shakouri, T., et al. (2022) · Neuron · doi:10.1016/j.neuron.2022.06.021 · Cited by 262
Cerebellar nuclei evolved by repeatedly duplicating a conserved cell-type set
Kebschull, J. M., Richman, E. B., Ringach, N., Friedmann, D., Albarran, E., Kolluru, S. S., Jones, R. C., Allen, W. E., Wang, Y., Cho, S. W., et al. (2020) · Science · doi:10.1126/science.abd5059 · Cited by 262
“2020) and species (Hodge et al. 2019; Bakken et al. 2020; Boldog et al. 2018; Hodge et al. 2020; Tosches et al. 2018; Krienen et al. 2019; Peng et al. 2019; Hoang et al. 2019; Norimoto et al. 2020; Khrameeva et al. 2020) in a system that contains different numbers of homologous regions in”
BackgroundMolecular and cellular evolution of the primate dorsolateral prefrontal cortex
Ma, S., Škarica, M., Li, Q., Xu, C., Risgaard, R. D., Tebbenkamp, A. T. N., Mato-Blanco, X., Kovner, R., Krsnik, Ž., de Martin, X., et al. (2022) · Science · doi:10.1126/science.abo7257 · Cited by 257
“S15A), which has higher sequencing depth using SMART-seq (16).”
BackgroundMethodResultInfluentialConnectomic comparison of mouse and human cortex
Loomba, S., Straehle, J., Gangadharan, V., Heike, N., Khalifa, A., Motta, A., Ju, N., Sievers, M., Gempt, J., Meyer, H. S., et al. (2022) · Science · doi:10.1126/science.abo0924 · Cited by 242
Marton, R. M., & Pașca, S. P. (2019) · Trends in Cell Biology · doi:10.1016/j.tcb.2019.11.004 · Cited by 253
“neuronal subtypes or astrocytes that may influence how these cells interact [7,8].”
BackgroundVirtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Disorder, A. S., Disorder, B., Disorder, M. D., Disorder, O.-C., Groups, A. S. E. W., Patel, Y., Parker, N., Shin, J., Howard, D., French, L., et al. (2020) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.2694 · Cited by 252
Automated methods for cell type annotation on scRNA-seq data
Pasquini, G., Rojo Arias, J. E., Schäfer, P., & Busskamp, V. (2021) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2021.01.015 · Cited by 249
“One task likely to be significantly more challenging is the identification of cell subtypes, for example within the neuronal classes, as only few genes may be crucial for their discrimination [57].”
BackgroundUzquiano, A., Kedaigle, A. J., Pigoni, M., Paulsen, B. D. S., Adiconis, X., Kim, K., Faits, T., Nagaraja, S., Antón-Bolaños, N., Gerhardinger, C., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.010 · Cited by 257
Harmonized cross-species cell atlases of trigeminal and dorsal root ganglia
Bhuiyan, S. A., Xu, M., Yang, L., Semizoglou, E., Bhatia, P., Pantaleo, K. I., Tochitsky, I., Jain, A., Erdoğan, B., Blair, S. J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adj9173 · Cited by 260
Herring, C. A., Simmons, R. K., Freytag, S., Poppe, D., Moffet, J. J. D., Pflueger, J., Buckberry, S., Vargas-Landín, D. B., Clément, O., Goñi, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.039 · Cited by 242
“In contrast, L2/3-CUX2 and L5/6-THEMIS show maximum eigentrend values after birth, reflecting the increasing concentration of local projections at this time (Kostovi c et al., 2019).”
InfluentialThe diversity of GABAergic neurons and neural communication elements
Huang, Z. J., & Paul, A. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0195-4 · Cited by 201
Human brain organogenesis: Toward a cellular understanding of development and disease
Kelley, K. W., & Pașca, S. P. (2021) · Cell · doi:10.1016/j.cell.2021.10.003 · Cited by 244
“This contrasts with comparative adult brain single-cell gene expression analyses, which have identified substantial changes among homologous cell types in human, non-human primates, and rodents (Hodge et al., 2019; Krienen et al., 2020; Bakken et al., 2021).”
BackgroundResultSingle-cell spatial transcriptome reveals cell-type organization in the macaque cortex
Chen, A., Sun, Y., Lei, Y., Li, C., Liao, S., Meng, J., Bai, Y., Liu, Z., Liang, Z., Zhu, Z., et al. (2023) · Cell · doi:10.1016/j.cell.2023.06.009 · Cited by 232
DSTG: deconvoluting spatial transcriptomics data through graph-based artificial intelligence
Song, Q., & Su, J. (2020) · Briefings in Bioinformatics · doi:10.1093/bib/bbaa414 · Cited by 229
Pfisterer, U., Petukhov, V., Demharter, S., Meichsner, J., Thompson, J. J., Batiuk, M. Y., Asenjo-Martínez, A., Vasistha, N. A., Thakur, A., Mikkelsen, J. D., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18752-7 · Cited by 238
Computational Models of Interoception and Body Regulation
Petzschner, F. H., Garfinkel, S. N., Paulus, M. P., Koch, C., & Khalsa, S. S. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.012 · Cited by 227
“In addition, while there are increasingly large-scale endeavors, like the cell census effort of the BRAIN initiative (www.biccn.org), to map and specify cell types in the various brain regions across species [90], there are currently no parallel endeavors for a functional map of the PNS.”
BackgroundGoetz, J. J., Jessen, Z. F., Jacobi, A., Mani, A., Cooler, S., Greer, D., Kadri, S., Segal, J. P., Shekhar, K., Sanes, J. R., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2022.111040 · Cited by 224
Clarke, Z. A., Andrews, T. S., Atif, J., Pouyabahar, D., Innes, B. T., MacParland, S. A., & Bader, G. D. (2021) · Nature Protocols · doi:10.1038/s41596-021-00534-0 · Cited by 234
“Typically, one-to-one orthologs are used 100,121 , which better ensures the conservation of function, although it is possible to use one-to-many and many-to-many relationships to increase gene coverage.”
BackgroundLu, T. M., Houghton, S., Magdeldin, T., Durán, J. G. B., Minotti, A. P., Snead, A. M., Sproul, A. A., Nguyen, D.-H. T., Xiang, J., Fine, H. A., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2016950118 · Cited by 224
“All samples were generated and sequenced by our group with the exception of two brain EC samples and one choroid plexus sample acquired from the Allen Institute Brain Map (37, 38) and Pellegrini et al. (39), respectively.”
Tran, M. N., Maynard, K. R., Spangler, A., Huuki, L. A., Montgomery, K. D., Sadashivaiah, V., Tippani, M., Barry, B. K., Hancock, D. B., Hicks, S. C., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.09.001 · Cited by 219
Spatial and cell type transcriptional landscape of human cerebellar development
Aldinger, K. A., Thomson, Z., Phelps, I. G., Haldipur, P., Deng, M., Timms, A. E., Hirano, M., Santpere, G., Roco, C. M., Rosenberg, A. B., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00872-y · Cited by 215
Rewiring of human neurodevelopmental gene regulatory programs by human accelerated regions
Girskis, K. M., Stergachis, A. B., DeGennaro, E. M., Doan, R. N., Qian, X., Johnson, M. B., Wang, P. P., Sejourne, G. M., Nagy, M. A., Pollina, E. A., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.08.005 · Cited by 193
“Longer cell cycles are thought to reduce the rate of somatic mutation or maintain DNA quality control and may facilitate formation of the remarkable diversity of neuronal types that constitute the human brain (Boldog et al., 2018; Hodge et al., 2019), but they come at the potential cost of increasing heterochrony, a l…”
BackgroundJung, M., Dourado, M., Maksymetz, J., Jacobson, A. R., Laufer, B. I., Baca, M., Foreman, O., Hackos, D. H., Riol‐Blanco, L., & Kaminker, J. S. (2023) · Nature Communications · doi:10.1038/s41467-023-36014-0 · Cited by 219
Comparative transcriptomics reveals human-specific cortical features
Jorstad, N. L., Song, J. H. T., Exposito-Alonso, D., Suresh, H., Castro-Pacheco, N., Krienen, F. M., Yanny, A. M., Close, J., Gelfand, E., Long, B., et al. (2023) · Science · doi:10.1126/science.ade9516 · Cited by 208
Self-citationEarly Alzheimer’s disease pathology in human cortex involves transient cell states
Gazestani, V., Kamath, T., Nadaf, N. M., Dougalis, A., Burris, S. J., Rooney, B., Junkkari, A., Vanderburg, C., Pelkonen, A., Gomez-Budia, M., et al. (2023) · Cell · doi:10.1016/j.cell.2023.08.005 · Cited by 209
Transcriptomic cytoarchitecture reveals principles of human neocortex organization
Jorstad, N. L., Close, J., Johansen, N., Yanny, A. M., Barkan, E. R., Travaglini, K. J., Bertagnolli, D., Campos, J., Casper, T., Crichton, K., et al. (2023) · Science · doi:10.1126/science.adf6812 · Cited by 209
“However, cortical areas differ in positional topography, shape and size, laminar and columnar organization, and neuron proportions ( 8 – 10 ).”
BackgroundSelf-citationSingle-cell analysis of prenatal and postnatal human cortical development
Velmeshev, D., Perez, Y., Yan, Z., Valencia, J. E., Castaneda-Castellanos, D. R., Wang, L., Schirmer, L., Mayer, S., Wick, B., Wang, S., et al. (2023) · Science · doi:10.1126/science.adf0834 · Cited by 204
Ayhan, F., Kulkarni, A., Berto, S., Sivaprakasam, K., Douglas, C., Lega, B. C., & Konopka, G. (2021) · Neuron · doi:10.1016/j.neuron.2021.05.003 · Cited by 207
Metadata
- Authors
- Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., Yao, Z., Eggermont, J., Höllt, T., Levi, B. P., Shehata, S. I., Aevermann, B., Beller, A., Bertagnolli, D., Brouner, K., Casper, T., Cobbs, C., Dalley, R., Dee, N., Ding, S.-L., Ellenbogen, R. G., Fong, O., Garren, E., Goldy, J., Gwinn, R. P., Hirschstein, D., Keene, C. D., Keshk, M., Ko, A. L., Lathia, K., Mahfouz, A., Maltzer, Z., McGraw, M., Nguyen, T. N., Nyhus, J., Ojemann, J. G., Oldre, A., Parry, S., Reynolds, S., Rimorin, C., Shapovalova, N. V., Somasundaram, S., Szafer, A., Thomsen, E. R., Tieu, M., Quon, G., Scheuermann, R. H., Yuste, R., Sunkin, S. M., Lelieveldt, B., Feng, D., Ng, L., Bernard, A., Hawrylycz, M., Phillips, J. W., Tasic, B., Zeng, H., Jones, A. R., Koch, C., & Lein, E. S.
- Affiliations
- Allen Institute for Brain Science (US)
- University of California, Davis (US)
- Leiden University Medical Center (NL)
- J. Craig Venter Institute (US)
- University of Washington (US)
- Swedish Medical Center (US)
- Columbia University (US)
- Corresponding author
- Lein, Ed S.
- ORCID
- Hodge, Rebecca D.
- Bakken, Trygve E.
- Miller, Jeremy A.
- Smith, Kimberly A.
- Barkan, Eliza R.
- Graybuck, Lucas T.
- Close, Jennie L.
- Long, Brian
- Johansen, Nelson
- Yao, Zizhen
- Eggermont, Jeroen
- Höllt, Thomas
- Levi, Boaz P.
- Shehata, Soraya I.
- Aevermann, Brian
- Beller, Allison
- Bertagnolli, Darren
- Brouner, Krissy
- Casper, Tamara
- Cobbs, Charles
- Dalley, Rachel
- Dee, Nick
- Ding, Song-Lin
- Ellenbogen, Richard G.
- Fong, Olivia
- Goldy, Jeff
- Gwinn, Ryder P.
- Hirschstein, Daniel
- Keene, C. Dirk
- Ko, Andrew L.
- Lathia, Kanan
- Mahfouz, Ahmed
- Maltzer, Zoe
- Nguyen, Thuc Nghi
- Nyhus, Julie
- Ojemann, Jeffrey G.
- Oldre, Aaron
- Rimorin, Christine
- Shapovalova, Nadiya V.
- Somasundaram, Saroja
- Szafer, Aaron
- Thomsen, Elliot R.
- Tieu, Michael
- Quon, Gerald
- Scheuermann, Richard H.
- Yuste, Rafael
- Sunkin, Susan M.
- Lelieveldt, Boudewijn
- Feng, David
- Ng, Lydia
- Bernard, Amy
- Hawrylycz, Michael
- Phillips, John W.
- Tasic, Bosiljka
- Zeng, Hongkui
- Lein, Ed S.
- Venue
- Nature
- Published
- 2019-08-21
- Volume
- 573
- Issue
- 7772
- Pages
- 61-68
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6919571
- OpenAlex
- W2969948459
- Cited by
- 1,775
- References
- 89
- Citations by year
- 2026: 199 · 2025: 242 · 2024: 275 · 2023: 269 · 2022: 235 · 2021: 289 · 2020: 212 · 2019: 43
- FWCI
- 64.09
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of Washington
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (12720, 12721)
- National Institutes of Health (5u01mh114812-03, MH114812-02)
- National Institute of Mental Health (U01MH105982, U01MH114812, U19MH114830)
- National Institute of General Medical Sciences (T32GM008497)
- 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 › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- human cerebral cortex, middle temporal gyrus, cortical cell types, excitatory neurons, inhibitory neurons, single-nucleus RNA sequencing, human-mouse comparison, cortical laminar organization, species differences, neuronal morphology, gene expression
- MeSH terms
- RNA-Seq, Adolescent, Adult, Aged, Animals, Astrocytes, Cerebral Cortex, Biological Evolution, Female, Humans, Male, Middle Aged, Neural Inhibition, Neurons, Species Specificity, Principal Component Analysis, Mice, Young Adult, Single-Cell Analysis, Transcriptome
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