Comparative transcriptomics reveals human-specific cortical features
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Abstract
Abstract Humans have unique cognitive abilities among primates, including language, but their molecular, cellular, and circuit substrates are poorly understood. We used comparative single nucleus transcriptomics in adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets from the middle temporal gyrus (MTG) to understand human-specific features of cellular and molecular organization. Human, chimpanzee, and gorilla MTG showed highly similar cell type composition and laminar organization, and a large shift in proportions of deep layer intratelencephalic-projecting neurons compared to macaque and marmoset. Species differences in gene expression generally mirrored evolutionary distance and were seen in all cell types, although chimpanzees were more similar to gorillas than humans, consistent with faster divergence along the human lineage. Microglia, astrocytes, and oligodendrocytes showed accelerated gene expression changes compared to neurons or oligodendrocyte precursor cells, indicating either relaxed evolutionary constraints or positive selection in these cell types. Only a few hundred genes showed human-specific patterning in all or specific cell types, and were significantly enriched near human accelerated regions (HARs) and conserved deletions (hCONDELS) and in cell adhesion and intercellular signaling pathways. These results suggest that relatively few cellular and molecular changes uniquely define adult human cortical structure, particularly by affecting circuit connectivity and glial cell function.
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BICCN and BICAN reference classifications provide a foundational reference to understand the cellular, molecular and epigenomic underpinnings of AD.
“These reference classifications provide an extremely powerful foundational reference to understand the cellular, molecular and epigenomic underpinnings of AD.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [18]
The Within-species cell type taxonomies section describes cortical cell-type classifications, and the Discussion says the data are a resource for future investigation of disease-associated gene programs. The paper does not specifically establish these classifications as a reference for understanding Alzheimer’s disease or its epigenomic underpinnings. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe study profiled 3.4 million high-quality nuclei across all modalities, mapping each to one of 139 molecular cell types from an expanded BRAIN Initiative MTG cellular taxonomy that included disease-associated states.
“We collectively profiled 3.4 million high-quality nuclei across all modalities, mapping each to one of 139 molecular cell types from an expanded BRAIN Initiative MTG cellular taxonomy18 that included disease-associated states.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [18]
The Within-species cell type taxonomies section describes an expanded human MTG taxonomy, supporting the citation’s identification of a taxonomy. It reports 151 human clusters, not 139 molecular cell types, and does not describe disease-associated states. The 3.4 million nuclei are presented as the citing authors’ own profiling, not a result attributed to this source. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBrains were collected using highly optimized brain preparation methods with a mean postmortem interval of 7.0 h that enable exceptionally high-quality snRNA-seq, snATAC-seq and MERFISH profiling.
“Brains were collected using highly optimized brain preparation methods (mean postmortem interval = 7.0 h; Extended Data Fig. 1b) that enable exceptionally high-quality snRNA-seq, snATAC–seq and MERFISH profiling17–19,23,36,37.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [18]
The Methods sections on tissue specimens, single-nucleus RNA sequencing, and in situ gene-expression profiling describe preparation of postmortem human brain tissue for snRNA-seq and MERFISH; page numbers are unavailable in our copy. They do not report a mean postmortem interval of 7.0 hours or establish that these methods enabled snATAC-seq profiling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn MTG snRNA-seq data, NPAS3 is differentially expressed in several neuronal types when comparing human and chimpanzee samples.
“In this dataset, we found that NPAS3 is differentially expressed in several neuronal types when comparing human and chimpanzee samples (Jorstad et al. 2023).”
From The Human Accelerated Region HAR202 Controls <i>NPAS3</i> Expression in the Developing Forebrain Displaying Differential Enhancer Activity Between Modern and Archaic Human Sequences (2024) · cites this paper as Jorstad et al. 2023
Both Oligo_2 and Oligo_4 supertypes are found throughout the cortical column in the BRAIN Initiative reference dataset.
“both supertypes are found throughout the cortical column in the BRAIN Initiative reference dataset18.”
From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [18]
The Within-species cell type taxonomies section describes oligodendrocytes and says that human MTG cell-type distributions were summarized by cortical depth. The passages found by searching for Oligo_2, Oligo_4, and the BRAIN Initiative reference dataset do not identify those supertypes or say that both occur throughout the cortical column. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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Cites
Comprehensive Integration of Single-Cell Data
Stuart, T., Butler, A., Hoffman, P., Hafemeister, C., Papalexi, E., Mauck, W. M., Hao, Y., Stoeckius, M., Smibert, P., & Satija, R. (2019) · Cell · doi:10.1016/j.cell.2019.05.031 · Cited by 15,453 · see citing works
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442 · cited 1× · see citing works
“This raises the possibility that decreased enhancer activity from HARsv2_1818 in humans may have decreased PTPRG expressionspecificallyintheexcitatory neuron consensus type L5 ET_2 and that separateregulatorymechanismsmaydecrease PTPRG expression in microglia and specific inhibitory neuron…”
BackgroundMcGinnis, C. S., Murrow, L. M., & Gartner, Z. J. (2019) · Cell Systems · doi:10.1016/j.cels.2019.03.003 · Cited by 4,521 · see citing works
GREAT improves functional interpretation of cis-regulatory regions
McLean, C. Y., Bristor, D., Hiller, M., Clarke, S. L., Schaar, B. T., Lowe, C. B., Wenger, A. M., & Bejerano, G. (2010) · Nature Biotechnology · doi:10.1038/nbt.1630 · Cited by 4,502 · see citing works
Hafemeister, C., & Satija, R. (2019) · Genome Biology · doi:10.1186/s13059-019-1874-1 · Cited by 4,479 · cited 2× · see citing works
“Nuclei were normalized using SCTransform ( 19 ), and neighborhoods were integrated together within a species and across individuals and modalities by identifying mutual nearest neighbor anchors and applying canonical correlation analysis as implemented in Seurat ( 18 ).”
MethodEvo-Devo and an Expanding Evolutionary Synthesis: A Genetic Theory of Morphological Evolution
Carroll, S. B. (2008) · Cell · doi:10.1016/j.cell.2008.06.030 · Cited by 2,067 · cited 1× · see citing works
“studies of genome sequence evolution in humans and other species that estimated that more than 80% of adaptive sequence change is likely regulatory (44, 69, 70).”
BackgroundMolecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,847 · cited 2× · see citing works
“Whenthepedalwith-drawal reflex was eliminated and/or the respiratory rate was diminished, animals were transcar-dially perfused with ice-cold sucrose-HEPES buffer ( 78 ).”
MethodThe genomic basis of adaptive evolution in threespine sticklebacks
Jones, F. C., Grabherr, M. G., Chan, Y. F., Russell, P. H., Mauceli, E., Johnson, J., Swofford, R., Pirun, M., Zody, M. C., White, S. J., et al. (2012) · Nature · doi:10.1038/nature10944 · Cited by 1,792 · see citing works
Conserved cell types with divergent features in human versus mouse cortex
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., et al. (2019) · Nature · doi:10.1038/s41586-019-1506-7 · Cited by 1,775 · see citing works
Self-citationA taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
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., et al. (2021) · Cell · doi:10.1016/j.cell.2021.04.021 · Cited by 1,065 · see citing works
SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse
Koopmans, F., van Nierop, P., Andres-Alonso, M., Byrnes, A., Cijsouw, T., Coba, M. P., Cornelisse, L. N., Farrell, R. J., Goldschmidt, H. L., Howrigan, D. P., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.05.002 · Cited by 938 · cited 3× · see citing works
“Byperforminggenesetenrich-mentanalysisusingSynGO( 28 ), we found a significant enrichment of hDEGs among SynGO genes compared with all expressed genes ( P 10 − 16 ) and a further enrichment of hDEGs near HARs and hCONDELs among SynGO genes compared with all hDEGs ( P 10 − 5 ) (Fig.”
BackgroundMethodInfluentialThe evolution of distributed association networks in the human brain
Buckner, R. L., & Krienen, F. M. (2013) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2013.09.017 · Cited by 836 · see citing works
Self-citationBrain cell type–specific enhancer–promoter interactome maps and disease <b>-</b> risk association
Nott, A., Holtman, I. R., Coufal, N. G., Schlachetzki, J. C. M., Yu, M., Hu, R., Han, C. Z., Pena, M., Xiao, J., Wu, Y., et al. (2019) · Science · doi:10.1126/science.aay0793 · Cited by 823 · see citing works
Comparative cellular analysis of motor cortex in human, marmoset and mouse
Bakken, T. E., Jorstad, N. L., Hu, Q., Lake, B. B., Tian, W., Kalmbach, B. E., Crow, M., Hodge, R. D., Krienen, F. M., Sorensen, S. A., et al. (2021) · Nature · doi:10.1038/s41586-021-03465-8 · Cited by 812 · see citing works
Spreading of pathology in neurodegenerative diseases: a focus on human studies
Brettschneider, J., Tredici, K. D., Lee, V. M.-Y., & Trojanowski, J. Q. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3887 · Cited by 790 · see citing works
EphB Receptors Interact with NMDA Receptors and Regulate Excitatory Synapse Formation
Dalva, M. B., Takasu, M. A., Lin, M. Z., Shamah, S. M., Hu, L. S., Gale, N. W., & Greenberg, M. E. (2000) · Cell · doi:10.1016/s0092-8674(00)00197-5 · Cited by 716 · cited 1× · see citing works
“Importantly, ephrin/EPH receptor signaling has been shown to promote synaptogenesis in the mouse developing cortex (54, 55).”
BackgroundWidespread intron retention in mammals functionally tunes transcriptomes
Braunschweig, U., Barbosa-Morais, N. L., Pan, Q., Nachman, E. N., Alipanahi, B., Gonatopoulos-Pournatzis, T., Frey, B., Irimia, M., & Blencowe, B. J. (2014) · Genome Research · doi:10.1101/gr.177790.114 · Cited by 664 · see citing works
Heterogeneity of astrocytic form and function.
Oberheim, N. A., Goldman, S. A., & Nedergaard, M. (2012) · Methods in Molecular Biology · doi:10.1007/978-1-61779-452-0_3 · Cited by 638 · cited 1× · see citing works
“In addition to well-described changes in the number and function of neurons in the human brain (71), many non-neuronal cell types also undergo comparable changes in the human lineage (72, 73).”
BackgroundMapping single-cell data to reference atlases by transfer learning
Lotfollahi, M., Naghipourfar, M., Luecken, M. D., Khajavi, M., Büttner, M., Wagenstetter, M., Avsec, Ž., Gayoso, A., Yosef, N., Interlandi, M., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01001-7 · Cited by 602 · cited 1× · see citing works
“For each of the five cell-type neighborhoods(non-neuronal,MGE-andCGE-derivedinterneurons,andIT-andnon-IT-projectingexcitatoryneurons),webuilta referencewithfourprimatedatasetsandused thefifthprimatedatasetasqueryforcelltype annotationusingscArches( 40 ).”
BackgroundHuman-specific loss of regulatory DNA and the evolution of human-specific traits
McLean, C. Y., Reno, P. L., Pollen, A. A., Bassan, A. I., Capellini, T. D., Guenther, C., Indjeian, V. B., Lim, X., Menke, D. B., Schaar, B. T., et al. (2011) · Nature · doi:10.1038/nature09774 · Cited by 535 · cited 3× · see citing works
“…across mammals and have higher substitution rates in the human lineage ( 14 ), (ii) hCONDELs that are highly conserved across mammals and deleted in humans ( 45 , 46 ), and (iii) human ancestor quickly evolved regions (HAQERs) that are the fastest evolved regions in the human genome ( 47 ).”
BackgroundResultCortical Evolution: Judge the Brain by Its Cover
Geschwind, D. H., & Rakic, P. (2013) · Neuron · doi:10.1016/j.neuron.2013.10.045 · Cited by 519 · cited 1× · see citing works
“In addition to well-described changes in the number and function of neurons in the human brain (71), many non-neuronal cell types also undergo comparable changes in the human lineage (72, 73).”
BackgroundAstrocytic neuroligins control astrocyte morphogenesis and synaptogenesis
Stogsdill, J. A., Ramirez, J., Liu, D., Kim, Y. H., Baldwin, K. T., Enustun, E., Ejikeme, T., Ji, R.-R., & Eroglu, C. (2017) · Nature · doi:10.1038/nature24638 · Cited by 506 · see citing works
Molecular logic of cellular diversification in the mouse cerebral cortex
Di Bella, D. J., Habibi, E., Stickels, R. R., Scalia, G., Brown, J., Yadollahpour, P., Yang, S. M., Abbate, C., Biancalani, T., Macosko, E. Z., et al. (2021) · Nature · doi:10.1038/s41586-021-03670-5 · Cited by 464 · cited 1× · see citing works
“development have demonstrated the importance of these TFs in determining cell type identity where CUX2 is similarly expressed in L2/3 IT neurons and TSHZ2 is selectively expressed in L5 NP neurons (36).”
BackgroundCross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program
Geirsdottir, L., David, E., Keren-Shaul, H., Weiner, A., Bohlen, S. C., Neuber, J., Balic, A., Giladi, A., Sheban, F., Dutertre, C.-A., et al. (2019) · Cell · doi:10.1016/j.cell.2019.11.010 · Cited by 461 · see citing works
Microglia and early brain development: An intimate journey
Thion, M. S., Ginhoux, F., & Garel, S. (2018) · Science · doi:10.1126/science.aat0474 · Cited by 440 · cited 1× · see citing works
“Wenext examined gene expression changes in microglia, which also play critical roles in cortical circuit formation ( 31 , 32 ).”
BackgroundMorphological diversity of single neurons in molecularly defined cell types
Peng, H., Xie, P., Liu, L., Kuang, X., Wang, Y., Qu, L., Gong, H., Jiang, S., Li, A., Ruan, Z., et al. (2021) · Nature · doi:10.1038/s41586-021-03941-1 · Cited by 417 · cited 1× · see citing works
“High-CUX2 neuronsareselectivelyenriched in language-related regions in the human temporal and parietal cortex (MTG, A1, and ANG) ( 21 ), and these neurons may have distinct connectivity and contribute to the functional specializations of these regions.”
BackgroundscCODA is a Bayesian model for compositional single-cell data analysis
Büttner, M., Ostner, J., Müller, C. L., Theis, F. J., & Schubert, B. (2021) · Nature Communications · doi:10.1038/s41467-021-27150-6 · Cited by 388 · cited 2× · see citing works
“S14A) ( 43 ).”
BackgroundInnovations present in the primate interneuron repertoire
Krienen, F. M., Goldman, M., Zhang, Q., C. H. del Rosario, R., Florio, M., Machold, R., Saunders, A., Levandowski, K., Zaniewski, H., Schuman, B., et al. (2020) · Nature · doi:10.1038/s41586-020-2781-z · Cited by 381 · cited 2× · see citing works
“Similarly, snRNA-seq data collected from six additional regions of the marmoset cortex ( 10 , 12 , 22 ) revealedthatthehigh-CUX2 subtypewasmost enriched in temporal areas (MTG and A1) and less enriched in S1 (Fig.”
BackgroundMethodSelf-citationAstrocytes regulate cortical state switching in vivo
Poskanzer, K. E., & Yuste, R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520759113 · Cited by 377 · see citing works
Innovations in Primate Interneuron Repertoire
Krienen, F. M., Goldman, M., Zhang, Q., del Rosario, R., Florio, M., Machold, R., Saunders, A., Levandowski, K., Zaniewski, H., Schuman, B., et al. (2019) · doi:10.1101/709501 · Cited by 372 · see citing works
Self-citationCrow, M., Paul, A., Ballouz, S., Huang, Z. J., & Gillis, J. (2018) · Nature Communications · doi:10.1038/s41467-018-03282-0 · Cited by 365 · see citing works
Self-citationHigh-resolution comparative analysis of great ape genomes
Kronenberg, Z. N., Fiddes, I. T., Gordon, D., Murali, S., Cantsilieris, S., Meyerson, O. S., Underwood, J. G., Nelson, B. J., Chaisson, M. J. P., Dougherty, M. L., et al. (2018) · Science · doi:10.1126/science.aar6343 · Cited by 350 · cited 2× · see citing works
“…across mammals and have higher substitution rates in the human lineage ( 14 ), (ii) hCONDELs that are highly conserved across mammals and deleted in humans ( 45 , 46 ), and (iii) human ancestor quickly evolved regions (HAQERs) that are the fastest evolved regions in the human genome ( 47 ).”
BackgroundSardi, S. P., Murtie, J. C., Koirala, S., Patten, B. A., & Corfas, G. (2006) · Cell · doi:10.1016/j.cell.2006.07.037 · Cited by 349 · see citing works
GABA-Receptive Microglia Selectively Sculpt Developing Inhibitory Circuits
Favuzzi, E., Huang, S., Saldi, G.-A., Binan, L., Ibrahim, L. A., Fernández-Otero, M., Cao, Y., Zeine, A., Sefah, A., Zheng, K., et al. (2020) · Cell · doi:10.1016/j.cell.2021.06.018 · Cited by 321 · see citing works
The pyramidal cell in cognition: a comparative study in human and monkey
Elston, G. N., Benavides-Piccione, R., & DeFelipe, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-17-j0002.2001 · Cited by 317 · cited 10× · see citing works
“Human MTG is larger and more connected to other language-associatedcorticalareasthantheMTG ofchimpanzeesandotherNHPs( 3 – 5 ).”
BackgroundInfluentialTsai, N.-P., Wilkerson, J. R., Guo, W., Maksimova, M. A., DeMartino, G. N., Cowan, C. W., & Huber, K. M. (2012) · Cell · doi:10.1016/j.cell.2012.11.040 · Cited by 316 · cited 1× · see citing works
“Some studies have proposed roles in synapse elimination for members of highlydivergent synaptic families, including Pcdh10, ephrin-B1, and ephrin-A2 (56, 57).”
BackgroundBehaviorally consequential astrocytic regulation of neural circuits
Nagai, J., Yu, X., Papouin, T., Cheong, E., Freeman, M. R., Monk, K. R., Hastings, M. H., Haydon, P. G., Rowitch, D. H., Shaham, S., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.12.008 · Cited by 311 · see citing works
Microglia and the brain: Complementary partners in development and disease
Hammond, T. R., Robinton, D., & Stevens, B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100616-060509 · Cited by 288 · see citing works
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 · see citing works
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 · see citing works
Self-citationProtein tyrosine phosphatases PTPδ, PTPσ, and LAR: presynaptic hubs for synapse organization
Takahashi, H., & Craig, A. M. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.06.002 · Cited by 257 · see citing works
Margolis, S. S., Salogiannis, J., Lipton, D. M., Mandel-Brehm, C., Wills, Z. P., Mardinly, A. R., Hu, L., Greer, P. L., Bikoff, J. B., Ho, H.-Y. H., et al. (2010) · Cell · doi:10.1016/j.cell.2010.09.038 · Cited by 256 · cited 1× · see citing works
“Importantly,ephrin-EPHreceptorsig- nalinghasbeenshowntopromotesynapto-genesisinthemousedevelopingcortex( 57 , 58 ).”
Molecular 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 256 · cited 3× · see citing works
“In addition, human glia express more highly divergent genes than chimpanzee or gorilla glia, suggesting faster divergence of human microglia and astrocytes ( 9 ) as well as oligodendrocytes ( 8 ) among great apes.”
BackgroundResultMolecular and cellular reorganization of neural circuits in the human lineage
Sousa, A. M. M., Zhu, Y., Raghanti, M. A., Kitchen, R. R., Onorati, M., Tebbenkamp, A. T. N., Stutz, B., Meyer, K. A., Li, M., Kawasawa, Y. I., et al. (2017) · Science · doi:10.1126/science.aan3456 · Cited by 253 · cited 1× · see citing works
“Previous work reported the lack of tran- scriptandproteinexpressionoftyrosinehydrox-ylase( TH ), which encodes a key enzyme in the dopamine synthesis pathway, in the neocortex of non-human African great apes, including chimpanzees and gorillas ( 41 , 42 ).”
BackgroundChemico-genetic discovery of astrocytic control of inhibition in vivo
Takano, T., Wallace, J. T., Baldwin, K. T., Purkey, A., Uezu, A., Courtland, J. L., Soderblom, E. J., Shimogori, T., Maness, P. F., Eroğlu, Ç., et al. (2020) · Nature · doi:10.1038/s41586-020-2926-0 · Cited by 243 · cited 2× · see citing works
“To study synapse-related astrocytic gene programs, we used a molecular database of astrocyte cell-surface molecules enriched at astrocyte-neuron junctions from an in vivo proteomic labeling approach in the mouse cortex ( 29 ).”
MethodMenezes, M. J., McClenahan, F. K., Leiton, C. V., Aranmolate, A., Shan, X., & Colognato, H. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3678-13.2014 · Cited by 226 · cited 1× · see citing works
“Many species-specific DEGs were restricted to one or a few cell types, particularly for great apes (fig.”
BackgroundTranscriptomic 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 · cited 2× · see citing works
“OnthebasisofthesnRNA-seqdata thatwecollectedfromsevenadditionalre-gionsofthehumancortex( 21 ), low-CUX2 neurons were more common in many regions, and high-CUX2 neurons were enriched in temporal cortex (MTG and primary auditory, A1) and parietal cortex (angular gyrus, ANG and primary somatosensory,…”
BackgroundPyramidal Neurons in Prefrontal Cortex Receive Subtype-Specific Forms of Excitation and Inhibition
Lee, A. T., Gee, S. M., Vogt, D., Patel, T., Rubenstein, J. L., & Sohal, V. S. (2014) · Neuron · doi:10.1016/j.neuron.2013.10.031 · Cited by 201 · cited 2× · see citing works
“Because PVALB interneurons and excitatory neurons form cell type – specific patterns of connectivity ( 49 ), the differential expression of ephrins and EPH receptors could reflect primate species differences in the formation of inhibitory microcircuits that involve specific subtypes of PVALB…”
Kia, D. A., Zhang, D., Guelfi, S., Manzoni, C., Hubbard, L., Reynolds, R. H., Botía, J. A., Ryten, M., Ferrari, R., Lewis, P. A., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2020.5257 · Cited by 199 · see citing works
Hearing and seeing meaning in speech and gesture: insights from brain and behaviour
Özyürek, A. (2014) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0296 · Cited by 194 · see citing works
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 · cited 5× · see citing works
“PTPRG is located near HARsv2_1818 (chr3:61283266-61283416, hg38), which has decreased enhancer activity from the human sequence compared with that from the orthologous chimpanzee sequence ( 14 ).”
BackgroundMethodInfluentialDo stars govern our actions? Astrocyte involvement in rodent behavior
Oliveira, J. F., Sardinha, V. M., Guerra-Gomes, S., Araque, A., & Sousa, N. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.07.006 · Cited by 189 · cited 1× · see citing works
“Emerging evidence demonstrates the critical role that non-neuronal cell types play in cortical development, network function, and behavior ( 62 – 67 ).”
BackgroundStructure and regulation of the human INO80–nucleosome complex
Ayala, R., Willhöft, O., Aramayo, R. J., Wilkinson, M., McCormack, E. A., Ocloo, L., Wigley, D. B., & Zhang, X. (2018) · Nature · doi:10.1038/s41586-018-0021-6 · Cited by 189 · cited 1× · see citing works
“INO80B ( 24 )and SBNO1 are involved in chromatin remodeling, and SBNO1 contributes to brain-axis development in zebrafish ( 25 ) and is a risk gene for intellectual disability ( 26 ).”
BackgroundSingle-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons
Földy, C., Darmanis, S., Aoto, J., Malenka, R. C., Quake, S. R., & Südhof, T. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610155113 · Cited by 179 · see citing works
A genomic timescale for placental mammal evolution
Foley, N. M., Mason, V. C., Harris, A. J., Bredemeyer, K. R., Damas, J., Lewin, H. A., Eizirik, E., Gatesy, J., Karlsson, E. K., Lindblad‐Toh, K., et al. (2023) · Science · doi:10.1126/science.abl8189 · Cited by 173 · cited 1× · see citing works
“Onthe basisofarecentlypublishedmammalianphy-logeny( 13 ), this represents approximately 38 million years of evolution since these primate species shared a last common ancestor and encompasses the relatively recent divergence of the human lineage from that of chimpanzees at 6 million years ago.”
BackgroundKofuji, P., & Araque, A. (2021) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-101920-112225 · Cited by 166 · cited 1× · see citing works
“Emerging evidence demonstrates the critical role that non-neuronal cell types play in cortical development, network function, and behavior ( 62 – 67 ).”
BackgroundGABAergic signaling to astrocytes in the prefrontal cortex sustains goal-directed behaviors
Mederos, S., Sánchez‐Puelles, C., Esparza, J., Valero, M., Ponomarenko, A. A., & Perea, G. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00752-x · Cited by 163 · see citing works
Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts
Fellner, L., Jellinger, K. A., Wenning, G. K., & Stefanova, N. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0833-z · Cited by 162 · see citing works
Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains
Khrameeva, E., Kurochkin, I., Han, D., Guijarro, P., Kanton, S., Santel, M., Qian, Z., Rong, S., Mazin, P., Sabirov, M., et al. (2020) · Genome Research · doi:10.1101/gr.256958.119 · Cited by 162 · cited 1× · see citing works
“…has identified hundreds of genes with up-or down-regulated expression in the cortex of humans compared with that of chimpanzees and other primates ( 6 – 9 ) but have been limited to comparing broad populations of cells or have lacked another great ape species in which to study changes specific to…”
BackgroundArdesch, D. J., Scholtens, L. H., Li, L., Preuss, T. M., Rilling, J. K., & van den Heuvel, M. P. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818512116 · Cited by 152 · cited 1× · see citing works
“Human MTG is larger and more connected to other language-associatedcorticalareasthantheMTG ofchimpanzeesandotherNHPs( 3 – 5 ).”
BackgroundCell-type-specific 3D epigenomes in the developing human cortex
Song, M., Pebworth, M.-P., Yang, X., Abnousi, A., Fan, C., Wen, J., Rosen, J. D., Choudhary, M. N. K., Cui, X., Jones, I. R., et al. (2020) · Nature · doi:10.1038/s41586-020-2825-4 · Cited by 143 · cited 3× · see citing works
“…adaptive by establishing putative links be-tween human accelerated regions (HARs) and human conserved deletions (hCONDELs) and human expression specializations by leveraging recently generated datasets of the in vitro activity of HARs ( 14 ) and cell type – specific chromatin folding ( 15 , 16 ).”
BackgroundMethodComprehensive transcriptome analysis of neocortical layers in humans, chimpanzees and macaques
He, Z., Han, D., Efimova, O., Guijarro, P., Yu, Q., Oleksiak, A., Jiang, S., Anokhin, K. V., Velichkovsky, B. M., Grünewald, S., et al. (2017) · Nature Neuroscience · doi:10.1038/nn.4548 · Cited by 136 · see citing works
Population-level integration of single-cell datasets enables multi-scale analysis across samples
Donno, C. D., Hediyeh-zadeh, S., Moinfar, A. A., Wagenstetter, M., Zappia, L., Lotfollahi, M., & Theis, F. J. (2023) · Nature Methods · doi:10.1038/s41592-023-02035-2 · Cited by 125 · cited 1× · see citing works
“We built each reference dataset using 2000 highly variable genes, trained a model on the reference using scPoli ( 84 ), and mapped the query cells onto the reference data (fig.”
MethodPyramidal neuron subtype diversity governs microglia states in the neocortex
Stogsdill, J. A., Kim, K., Binan, L., Farhi, S. L., Levin, J. Z., & Arlotta, P. (2022) · Nature · doi:10.1038/s41586-022-05056-7 · Cited by 120 · see citing works
Adaptive sequence divergence forged new neurodevelopmental enhancers in humans
Mangan, R. J., Alsina, F. C., Mosti, F., Sotelo-Fonseca, J. E., Snellings, D. A., Au, E. H., Carvalho, J., Sathyan, L., Johnson, G. D., Reddy, T. E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.10.016 · Cited by 111 · see citing works
Roumazeilles, L., Eichert, N., Bryant, K., Folloni, D., Sallet, J., Vijayakumar, S., Foxley, S., Tendler, B. C., Jbabdi, S., Reveley, C., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000810 · Cited by 99 · see citing works
Cell adhesion molecules regulating astrocyte–neuron interactions
Tan, C. X., & Eroğlu, Ç. (2021) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2021.03.015 · Cited by 93 · cited 1× · see citing works
“In such a case, reduced expression of negative regulators of synaptic assembly in human neurons could lead to an enhanced ability to form synaptic connections, potentially underlying the greater number of synapses per neuron that are observed in the human cortex compared with that of NHPs ( 61 ).”
ResultMacroscale cortical organization and a default-like apex transmodal network in the marmoset monkey
Buckner, R. L., & Margulies, D. S. (2019) · Nature Communications · doi:10.1038/s41467-019-09812-8 · Cited by 84 · see citing works
Accelerated evolution of oligodendrocytes in the human brain
Berto, S., Mendizabal, I., Usui, N., Toriumi, K., Chatterjee, P., Douglas, C., Tamminga, C. A., Preuss, T. M., Yi, S. V., & Konopka, G. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1907982116 · Cited by 77 · cited 1× · see citing works
“In addition, human glia express more highly divergent genes than chimpanzee or gorilla glia, suggesting faster divergence of human microglia and astrocytes ( 9 ) as well as oligodendrocytes ( 8 ) among great apes.”
BackgroundThe Large-Scale Organization of Gestures and Words in the Middle Temporal Gyrus
Papeo, L., Agostini, B., & Lingnau, A. (2019) · Journal of Neuroscience · doi:10.1523/jneurosci.2668-18.2019 · Cited by 67 · cited 3× · see citing works
“For example, humans have the capacity for vocal learning that requires a highly interconnected set of brain regions, including the middle temporal gyrus (MTG) region of the neocortex that integrates multimodal sensory information and is critical for visual and auditory language comprehension (1, 2).”
BackgroundA marmoset brain cell census reveals regional specialization of cellular identities
Krienen, F. M., Levandowski, K. M., Zaniewski, H., del Rosario, R. C. H., Schroeder, M. E., Goldman, M., Wienisch, M., Lutservitz, A., Beja-Glasser, V. F., Chen, C., et al. (2023) · Science Advances · doi:10.1126/sciadv.adk3986 · Cited by 66 · cited 1× · see citing works
“Similarly, snRNA-seq data collected from six additional regions of the marmoset cortex ( 10 , 12 , 22 ) revealedthatthehigh-CUX2 subtypewasmost enriched in temporal areas (MTG and A1) and less enriched in S1 (Fig.”
MethodSharif, A., Duhem-Tonnelle, V., Allet, C., Baroncini, M., Loyens, A., Kerr-Conte, J. A., Collier, F., Blond, S., Ojeda, S. R., Junier, M., et al. (2008) · Glia · doi:10.1002/glia.20762 · Cited by 61 · see citing works
Invariant Synapse Density and Neuronal Connectivity Scaling in Primate Neocortical Evolution
Sherwood, C. C., Miller, S. B., Karl, M. T., Stimpson, C. D., Phillips, K. A., Jacobs, B., Hof, P. R., Raghanti, M. A., & Smaers, J. B. (2020) · Cerebral Cortex · doi:10.1093/cercor/bhaa149 · Cited by 60 · see citing works
p130CASIs Required for Netrin Signaling and Commissural Axon Guidance
Liu, G., Li, W., Gao, X., Li, X., Jürgensen, C., Park, H.-T., Shin, N.-Y., Yu, J., He, M., Hanks, S. K., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4616-06.2007 · Cited by 58 · cited 1× · see citing works
“BCAR1 is a scaffold protein that is a component of the netrin signaling pathway and is involvedinaxonguidance( 23 ).”
BackgroundKalirin and Trio: RhoGEFs in Synaptic Transmission, Plasticity, and Complex Brain Disorders
Paskus, J. D., Herring, B. E., & Roche, K. W. (2020) · Trends in Neurosciences · doi:10.1016/j.tins.2020.05.002 · Cited by 56 · cited 1× · see citing works
“S6F), including up-regulation of SNCA (encoding alpha-synuclein) and TMEM163 implicated in neurodegenerative disorders (32–34), and down-regulation of the synapse-related Rho guanine nucleotide-exchange factor Kalirin (KALRN) associated with neurodevelopmental and neuropsychiatric disorders (35) (Fig.”
BackgroundSuresh, H., Crow, M., Jorstad, N. L., Hodge, R. D., Lein, E. S., Dobin, A., Bakken, T. E., & Gillis, J. (2023) · Nature Ecology & Evolution · doi:10.1038/s41559-023-02186-7 · Cited by 55 · cited 1× · see citing works
“This is described in more detail in our companion manuscript ( 83 ).”
BackgroundSandau, U. S., Mungenast, A. E., McCarthy, J. B., Biederer, T., Corfas, G., & Ojeda, S. R. (2011) · Endocrinology · doi:10.1210/en.2010-1434 · Cited by 49 · see citing works
Transcriptomic insights into human brain evolution: acceleration, neutrality, heterochrony
Somel, M., Rohlfs, R. V., & Liu, X. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2014.09.001 · Cited by 48 · see citing works
Raghanti, M. A., Spocter, M. A., Stimpson, C. D., Erwin, J. M., Bonar, C. J., Allman, J. M., Hof, P. R., & Sherwood, C. C. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2008.10.058 · Cited by 42 · see citing works
Kranz, T. M., Harroch, S., Manor, O., Lichtenberg, P., Friedlander, Y., Seandel, M., Harkavy‐Friedman, J., Walsh‐Messinger, J., Dolgalev, I., Heguy, A., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.05.042 · Cited by 41 · cited 1× · see citing works
“Genetic variants in PTPRG have been associated with neuro-psychiatric disorders, and Ptprg mutant mice show memory deficits, supporting an impor-tantrolefor PTPRG incognitivefunction( 51 – 54 ).”
BackgroundAstrocytic Ephrin-B1 Controls Excitatory-Inhibitory Balance in Developing Hippocampus
Nguyen, A. Q., Sutley-Koury, S. N., Koeppen, J., Mina, K., Woodruff, S., Hanna, S., Vengala, A., Hickmott, P. W., Obenaus, A., & Ethell, I. M. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0413-20.2020 · Cited by 41 · cited 1× · see citing works
“Some studies have proposed roles in synapse elimination for members of highlydivergent synaptic families, including Pcdh10, ephrin-B1, and ephrin-A2 (56, 57).”
BackgroundScaling up reproducible research for single-cell transcriptomics using MetaNeighbor
Fischer, S., Crow, M., Harris, B. D., & Gillis, J. A. (2021) · Nature Protocols · doi:10.1038/s41596-021-00575-5 · Cited by 36 · cited 2× · see citing works
“12 ( 38 , 39 ) was used to provide a measure of neuronal and non-neuronal subclass and cluster replicability within and across species.”
MethodInfluentialDevelopmental loci harbor clusters of accelerated regions that evolved independently in ape lineages
Kostka, D., Holloway, A. K., & Pollard, K. S. (2018) · Molecular Biology and Evolution · doi:10.1093/molbev/msy109 · Cited by 32 · cited 1× · see citing works
“S16),whichsupportspreviousfindingsthat showthatacceleratedgenomicregionsindif-ferentprimatelineagesclusternearsimilar genes( 48 ).”
Evolution of regulatory signatures in primate cortical neurons at cell-type resolution
Kozlenkov, A., Vermunt, M. W., Apontes, P., Li, J., Hao, K., Sherwood, C. C., Hof, P. R., Ely, J. J., Wegner, M., Mukamel, E. A., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2011884117 · Cited by 30 · cited 1× · see citing works
“Human MTG is larger and more connected to other language-associatedcorticalareasthantheMTG ofchimpanzeesandotherNHPs( 3 – 5 ).”
BackgroundKranz, T. M., Berns, A., Shields, J., Rothman, K., Walsh‐Messinger, J., Goetz, R. R., Chao, M. V., & Malaspina, D. (2016) · EBioMedicine · doi:10.1016/j.ebiom.2016.03.008 · Cited by 27 · see citing works
Cressant, A., Dubreuil, V., Kong, J., Kranz, T. M., Lazarini, F., Launay, J., Callebert, J., Sap, J., Malaspina, D., Granon, S., et al. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4490-8 · Cited by 27 · see citing works
Genomic structural variants are linked with intellectual disability
Bulayeva, K., Lesch, K., Bulayev, O. A., Walsh, C. A., Glatt, S. J., Gurgenova, F., Omarova, J., Berdichevets, I. N., & Thompson, P. M. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1366-8 · Cited by 26 · cited 1× · see citing works
“INO80B ( 24 )and SBNO1 are involved in chromatin remodeling, and SBNO1 contributes to brain-axis development in zebrafish ( 25 ) and is a risk gene for intellectual disability ( 26 ).”
BackgroundFunction of strawberry notch family genes in the zebrafish brain development.
Takano, A., Zochi, R., Hibi, M., Terashima, T., & Katsuyama, Y. (2011) · PubMed · doi:10.24546/81002689 · Cited by 19 · see citing works
Turakhia, Y., Chen, H. I., Marcovitz, A., & Bejerano, G. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa550 · Cited by 12 · see citing works
Fang, R., Xia, C., Zhang, M., He, J., Close, J., Long, B., Miller, J. A., Lein, E. S., & Zhuang, X. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.01.466826 · Cited by 4 · cited 2× · see citing works
“neuropeptidergic signaling and related GPCRs and ligands, (6) families of neurotransmitter-gated receptors and other ligand-gated receptors (including glutamate ionotropic receptors), (7) Ras GTPase superfamily, (8) families of Ras GAP and GEF signaling molecules, (9) families of other regulatory molecules and structu…”
Background
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Research works printed but not linked: 3
- [22]Krienen FM, Levandowski KM, Zaniewski H, del Rosario RCH, Schroeder ME, Goldman M, Lutservitz A, Zhang Q, Li KX, Beja-Glasser VF, Sharma J, Shin TW, Mauermann A, Wysoker A, Nemesh J, Kashin S, Vergara J, Chelini G, Dimidschstein J, Berretta S, Boyden E, McCarroll SA, Feng G, A marmoset brain cell census reveals persistent influence of developmental origin on neurons. bioRxiv (2022), p. 2022.10.18.512442.
- [33]Fang R, Xia C, Close JL, Zhang M, He J, Huang Z, Halpern AR, Long B, Miller JA, Lein ES, Zhuang X, Conservation and divergence of cortical cell organization in human and mouse revealed by MERFISH. Science. 377, 56– 62 (2022). 35771910 PMC9262715
- [79]Paxinos G, Watson C, Petrides M, Rosa M, Tokuno H, The Marmoset Brain in Stereotaxic Coordinates (Elsevier Science, 2011).
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Sorted by citations
Transcriptomic diversity of cell types across the adult human brain
Siletti, K., Hodge, R., Mossi Albiach, A., Lee, K. W., Ding, S.-L., Hu, L., Lönnerberg, P., Bakken, T., Casper, T., Clark, M., et al. (2023) · Science · doi:10.1126/science.add7046 · Cited by 832 · see citing works
Integrated multimodal cell atlas of Alzheimer’s disease
Gabitto, M. I., Travaglini, K. J., Rachleff, V. M., Kaplan, E. S., Long, B., Ariza, J., Ding, Y., Mahoney, J. T., Dee, N., Goldy, J., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01774-5 · Cited by 397 · see citing works
“We collectively profiled 3.4 million high-quality nuclei across all modalities, mapping each to one of 139 molecular cell types from an expanded BRAIN Initiative MTG cellular taxonomy 18 that included disease-associated states.”
InfluentialSpatiotemporal omics for biology and medicine
Liu, L., Chen, A., Li, Y., Mulder, J., Heyn, H., & Xu, X. (2024) · Cell · doi:10.1016/j.cell.2024.07.040 · Cited by 239 · see citing works
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 · see citing works
“Entropy was higher for all neuronal than non-neuronal subclasses and did not differ between excitatory and inhibitory subclasses or across areas based on a two-way analysis of variance (ANOVA) followed by post-hoc Tukey HSD tests (Fig.”
MethodSingle-cell genomics and regulatory networks for 388 human brains
Emani, P. S., Liu, J. J., Clarke, D., Jensen, M., Warrell, J., Gupta, C., Meng, R., Lee, C.-Y., Xu, S., Dursun, C., et al. (2024) · Science · doi:10.1126/science.adi5199 · Cited by 168 · see citing works
Shaping the brain: The emergence of cortical structure and folding
Akula, S. K., Exposito-Alonso, D., & Walsh, C. A. (2023) · Developmental Cell · doi:10.1016/j.devcel.2023.11.004 · Cited by 97 · see citing works
“Additionally, aRGCs appear to transform their basal processes at gestational week 16.5 in humans (and during postnatal development in ferrets) to a shorter fiber that becomes truncated at the border with the oSVZ, referred to as ‘‘truncated’’ RGCs, with these truncated progenitors potentially…”
BackgroundInfluentialA suite of enhancer AAVs and transgenic mouse lines for genetic access to cortical cell types
Ben‐Simon, Y., Hooper, M. J., Narayan, S., Daigle, T. L., Dwivedi, D., Way, S. W., Oster, A., Stafford, D. A., Mich, J. K., Taormina, M. J., et al. (2025) · Cell · doi:10.1016/j.cell.2025.05.002 · Cited by 81 · see citing works
Molecular features driving cellular complexity of human brain evolution
Caglayan, E., Ayhan, F., Liu, Y., Vollmer, R. M., Oh, E., Sherwood, C. C., Preuss, T. M., Yi, S. V., & Konopka, G. (2023) · Nature · doi:10.1038/s41586-023-06338-4 · Cited by 67 · see citing works
Interindividual variation in human cortical cell type abundance and expression
Johansen, N., Somasundaram, S., Travaglini, K. J., Yanny, A. M., Shumyatcher, M., Casper, T., Cobbs, C., Dee, N., Ellenbogen, R. G., Ferreira, M. L., et al. (2023) · Science · doi:10.1126/science.adf2359 · Cited by 73 · see citing works
A marmoset brain cell census reveals regional specialization of cellular identities
Krienen, F. M., Levandowski, K. M., Zaniewski, H., del Rosario, R. C. H., Schroeder, M. E., Goldman, M., Wienisch, M., Lutservitz, A., Beja-Glasser, V. F., Chen, C., et al. (2023) · Science Advances · doi:10.1126/sciadv.adk3986 · Cited by 66 · see citing works
A molecular and cellular perspective on human brain evolution and tempo
Lindhout, F. W., Krienen, F. M., Pollard, K. S., & Lancaster, M. A. (2024) · Nature · doi:10.1038/s41586-024-07521-x · Cited by 70 · see citing works
The 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
“Jorstad dataset and Lake dataset 38,42,43 are used as two technical replications for the main analyses.”
Advances 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
Considerations for building and using integrated single-cell atlases
Hrovatin, K., Sikkema, L., Shitov, V. A., Heimberg, G., Shulman, M., Oliver, A. J., Mueller, M. F., Ibarra, I. L., Wang, H., Ramírez-Suástegui, C., et al. (2024) · Nature Methods · doi:10.1038/s41592-024-02532-y · Cited by 67 · see citing works
Liu, Z., Zhang, S., James, B. T., Galani, K., Mangan, R. J., Fass, S. B., Liang, C., Wagle, M. M., Boix, C. A., Tanigawa, Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.06.031 · Cited by 65 · see citing works
Single-cell dissection of the human blood-brain barrier and glioma blood-tumor barrier
Xie, Y., Yang, F., He, L., Huang, H., Chao, M., Cao, H., Hu, Y., Fan, Z., Zhai, Y., Zhao, W., et al. (2024) · Neuron · doi:10.1016/j.neuron.2024.07.026 · Cited by 60 · see citing works
Unraveling mechanisms of human brain evolution
Lancaster, M. A. (2024) · Cell · doi:10.1016/j.cell.2024.08.052 · Cited by 54 · see citing works
Suresh, H., Crow, M., Jorstad, N. L., Hodge, R. D., Lein, E. S., Dobin, A., Bakken, T. E., & Gillis, J. (2023) · Nature Ecology & Evolution · doi:10.1038/s41559-023-02186-7 · Cited by 55 · see citing works
“Readers are encouraged to refer to Jorstad et al. 26 for further details on RNA-seq processing, quality control and annotation.”
BackgroundMethodKim, S., Lee, J., Koh, I. G., Ji, J., Kim, H. J., Kim, E., Park, J., Park, J.-E., & An, J. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01328-6 · Cited by 44 · see citing works
“Large-scale studies such as the Brain Initiative Cell Census Network have substantially aided in constructing detailed brain maps using single-nucleus RNA-sequencing analysis 1 – 4 .”
Kim, M.-H., Radaelli, C., Thomsen, E. R., Monet, D., Chartrand, T., Jorstad, N. L., Mahoney, J. T., Taormina, M. J., Long, B., Baker, K. S., et al. (2023) · eLife · doi:10.7554/elife.81863 · Cited by 43 · see citing works
“We find that ELFN1 is expressed in all interneuron subclasses except PVALB neurons, and this pattern is conserved from mouse to human, suggesting a similar role in non-PVALB expressing interneurons from mouse to human ( Jorstad et al., 2022 ).”
Libé‐Philippot, B., Lejeune, A., Wierda, K. D. B., Louros, N. N., Erkol, E., Vlaeminck, I., Beckers, S., Gaspariunaite, V., Bilheu, A., Konstantoulea, K., et al. (2022) · Cell · doi:10.1016/j.cell.2023.11.028 · Cited by 43 · see citing works
Mapping human tissues with highly multiplexed RNA in situ hybridization
Kalhor, K., Chen, C.-J., Lee, H. S., Cai, M., Nafisi, M., Que, R. A., Palmer, C. R., Yuan, Y., Zhang, Y., Li, X., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-46437-y · Cited by 38 · see citing works
“Of note, L6 IT Car3cells seem tobepositioned more super fi cially thanthe L6 IT population, consistent with recent observations in human visual cortex and middle temporal gyrus 61,62 (Fig.”
de Sousa, A. A., Beaudet, A., Calvey, T., Bardo, A., Benoît, J., Charvet, C. J., Dehay, C., Gómez‐Robles, A., Gunz, P., Heuer, K., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04803-4 · Cited by 37 · see citing works
Making Ramón y Cajal proud: Development of cell identity and diversity in the cerebral cortex
Bella, D. J. D., Domıńguez-Iturza, N., Brown, J. R., & Arlotta, P. (2024) · Neuron · doi:10.1016/j.neuron.2024.04.021 · Cited by 37 · see citing works
Delineating the effective use of self-supervised learning in single-cell genomics
Richter, T., Bahrami, M., Xia, Y., Fischer, D. S., & Theis, F. J. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-024-00934-3 · Cited by 36 · see citing works
Are we there yet? Exploring astrocyte heterogeneity one cell at a time
O’Dea, M. R., & Hasel, P. (2024) · Glia · doi:10.1002/glia.24621 · Cited by 27 · see citing works
Molecular signatures of cortical expansion in the human foetal brain
Ball, G., Oldham, S., Kyriakopoulou, V., Williams, L. Z. J., Karolis, V. R., Price, A. N., Hutter, J. M., Seal, M. L., Alexander‐Bloch, A. F., Hajnal, J. V., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54034-2 · Cited by 27 · see citing works
Pal, A., Noble, M. A., Morales, M., Pal, R., Baumgartner, M., Yang, J. W., Yim, K., Uebbing, S., & Noonan, J. P. (2025) · Cell · doi:10.1016/j.cell.2025.01.007 · Cited by 27 · see citing works
A transcriptomic atlas of astrocyte heterogeneity across space and time in mouse and marmoset
Schroeder, M. E., McCormack, D. M., Metzner, L. R., Kang, J., Li, K. X., Yu, E., Melamed, L., Levandowski, K. M., Zaniewski, H., Zhang, Q., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.09.011 · Cited by 26 · see citing works
Ciuba, K., Piotrowska, A., Chaudhury, D., Dehingia, B., Duński, E., Behr, R., Soroczyńska, K., Czystowska-Kuźmicz, M., Abbas, M., Bulanda, E., et al. (2025) · Cell Stem Cell · doi:10.1016/j.stem.2024.12.011 · Cited by 25 · 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
“First, although the transcriptomic divergence of homologous neurons is generally a function of their phylogenetic distance 107,109,116 , the rate of transcriptomic divergence is cell-type specific: in the primate cerebral cortex, for example, non-neuronal cells diverged more rapidly than neurons…”
The neuroscience of mental illness: Building toward the future
Gordon, J. A., Dzirasa, K., & Petzschner, F. H. (2024) · Cell · doi:10.1016/j.cell.2024.09.028 · Cited by 20 · see citing works
A family portrait of human brain cells
Weninger, A., & Arlotta, P. (2023) · Science · doi:10.1126/science.adk4857 · Cited by 18 · see citing works
Genomic, molecular, and cellular divergence of the human brain
Nehme, R., Pietiläinen, O. P. H., & Barrett, L. E. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.05.009 · Cited by 13 · see citing works
“…E:I ratio are implicated in multiple neuro-psychiatric and neurodegenerative conditions; for instance, it has been proposed that major depression is associated with a move toward inhibition, whereas autism, schizophrenia, and Alzheimer ’ s disease are associated with moves toward excitation [108].”
Werner, J. M., & Gillis, J. (2024) · PLoS Biology · doi:10.1371/journal.pbio.3002912 · Cited by 20 · see citing works
Accelerated cell-type-specific regulatory evolution of the human brain
Joshy, D. M., Santpere, G., & Yi, S. V. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2411918121 · Cited by 14 · see citing works
“A recent study demonstrated that while the number of DEGs in oligodendrocytes was similar between humans and chimpanzees, human oligodendrocyte DEGs exhibited larger expression differences ( 22 ).”
InfluentialDembrow, N. C., Sawchuk, S., Dalley, R. A., Opitz-Araya, X., Hudson, M., Radaelli, C., Alfiler, L., Walling-Bell, S., Bertagnolli, D., Goldy, J., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114718 · Cited by 13 · see citing works
“Because these datasets come from two different macaque species, we also analyzed human snRNA-seq datasets (Cv3 10×) from MCx (M1) 10 and TCx (MTG), 27 focusing on subclass and areal gene expression patterns conserved in macaque and human.”
Faravelli, I., Antón-Bolaños, N., Brown, J. R., & Arlotta, P. (2025) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-111522-014009 · Cited by 14 · see citing works
Neuronal Circuit Evolution: From Development to Structure and Adaptive SignificancePreprint
Konstantinides, N., & Desplan, C. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041493 · Cited by 12 · see citing works
Mapping human brain cell type origin and diseases through single-cell transcriptomics
Soorajkumar, A., Balan, B., Nassir, N., Akter, H., Shahin, Z., Berdiev, B. K., Woodbury‐Smith, M., Khalil, R., Cisse, B., Benamer, H. T. S., et al. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03562-6 · Cited by 13 · see citing works
“A comparative analysis of humans and our closest evolutionary relatives, chimpanzees and gorillas, reveals shared brain cell types with notable differences in the genes that regulate them [53].”
Spanaki, C., Sidiropoulou, K., Petraki, Z., Diskos, K., Konstantoudaki, X., Volitaki, E., Mylonaki, K., Savvaki, M., & Plaitakis, A. (2024) · iScience · doi:10.1016/j.isci.2024.108821 · Cited by 11 · see citing works
“Aspreviousstudies onhuman brain have shown that a high density of dendritic spines protects from age-related degeneration, 51 these observations, taken together, raise the possibility that the genetic enhancement of structural plasticity via GLUD2 may protect human brain from senescence, perhaps…”
BackgroundConserved Laminar-Cellular Architecture Predicts the Spectrolaminar MotifPreprint
Mulvey, A. G., Lichtenfeld, M. J., Nejat, H., Xiong, Y. S., Carlson, B. M., Mitchell, B., Mendoza-Halliday, D., Westerberg, J. A., Maier, A., Duque, A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.27.587084 · Cited by 11 · see citing works
Human-chimpanzee tetraploid system defines mechanisms of species-specific neural gene regulationPreprint
Song, J. H. T., Carter, A. C., Bushinsky, E. M., Beck, S. G., Petrocelli, J. E., Koreman, G. T., Babu, J., Kingsley, D. M., Greenberg, M. E., & Walsh, C. A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.31.646367 · Cited by 15 · see citing works
Cross-species consensus atlas of the primate basal gangliaPreprint
Johansen, N., Fu, Y., Schmitz, M. T., Dubuc, A., Kempynck, N., Wirthlin, M. E., Garcia, A. D., Hewitt, M. N., Turner, M. A., Seeman, S. C., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.15.694496 · Cited by 17 · see citing works
“Non-neuronal populations, especially microglia, were more divergent than neuronal cell types, in agreement with findings from primate neocortex 45,46 .”
Shen, Y., Shao, M., Hao, Z.-Z., Huang, M., Xu, N., & Liu, S. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-023-01160-4 · Cited by 11 · see citing works
“There are additional sub-classes such as the PAX6 [91, 98], LAMP5 LHX6 [10, 91, 98], and PAX6 ADARB2 (SNCG) [90, 98] subclasses originating from the CGE, and the PVALB UNC5B (Chandelier) [90, 98] and SST CHODL [90, 98] subclasses originating from the MGE.”
BackgroundReconstructing human-specific regulatory functions in model systems
Baumgartner, M., Ji, Y., & Noonan, J. P. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102259 · Cited by 10 · see citing works
Electric spiking activity in epithelial cells
Yu, S.-M., & Granick, S. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2427123122 · Cited by 10 · see citing works
“Given that neural spikes serve as the primary mode of communication between neurons and nonneuronal cell populations such as glial cells ( 12 ) and that in the field of neurobiology to analyze spike patterns allows one to gain insights into how the brain processes information, encodes memories, and…”
Starr, A. L., & Fraser, H. B. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf189 · Cited by 18 · see citing works
Generation of Mammalian Astrocyte Functional HeterogeneityPreprint
Bartels, T., Rowitch, D. H., & Bayraktar, O. A. (2024) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041351 · Cited by 11 · see citing works
MAPbrain: a multi-omics atlas of the primate brain
Zhuo, L., Wang, M., Song, T., Zhong, S., Zeng, B., Liu, Z., Zhou, X., Wang, W., Wu, Q., He, S., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae911 · Cited by 9 · see citing works
Multi-omic Characterization of HIV Effects at Single Cell Level across Human Brain RegionsPreprint
Yang, J., Agrawal, K., Stanley, J. S., Li, R., Jacobs, N., Wang, H., Lu, C. F., Qu, R., Clarke, D., Chen, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.02.05.636707 · Cited by 10 · see citing works
Caporale, A. L., Cinalli, A. R., Rubinstein, M., & Franchini, L. F. (2024) · Molecular Biology and Evolution · doi:10.1093/molbev/msae186 · Cited by 7 · see citing works
Han, C., Lin, S., Wang, Z., Cui, Y., Zou, Q., & Yuan, Z. (2025) · Nature Machine Intelligence · doi:10.1038/s42256-025-01097-5 · Cited by 8 · see citing works
Astrocyte Regional Specialization is Shaped by Postnatal DevelopmentPreprint
Schroeder, M. E., McCormack, D. M., Metzner, L. R., Kang, J., Li, K. X., Yu, E., Melamed, L., Levandowski, K. M., Zaniewski, H., Zhang, Q., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.10.11.617802 · Cited by 8 · see citing works
“This result underscores that evolutionary divergence of a cell type’s transcriptome unfolds at different rates across cell types 62,77,78 .”
Carter, A. C., Koreman, G. T., Petrocelli, J. E., Robb, J. E., Bushinsky, E. M., Trowbridge, S. K., Kingsley, D. M., Walsh, C. A., Song, J. H. T., & Greenberg, M. E. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.31.646366 · Cited by 11 · see citing works
“Recent advances in single-cell genomics have facilitated the identification of many gene expression di ff erences between primates, including humans, within specific cell types of the brain (Jorstad et al., 2023; Caglayan et al., 2023).”
A cross-species spatial transcriptomic atlas of the human and non-human primate basal gangliaPreprint
Hewitt, M. N., Turner, M. A., Johansen, N., McMillen, D., Dan, S., DeBerardine, M., Ruiz, A., Huang, M., Quon, J. S., Fu, Y., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.11.22.688128 · Cited by 10 · see citing works
Plaitakis, A., Sidiropoulou, K., Kotzamani, D., Litso, I., Zaganas, I. V., & Spanaki, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25105297 · Cited by 7 · see citing works
If you please, draw me a neuron — linking evolutionary tinkering with human neuron evolution
Libé‐Philippot, B., Polleux, F., & Vanderhaeghen, P. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102260 · Cited by 9 · see citing works
Preservation of co-expression defines the primary tissue fidelity of human neural organoidsPreprint
Werner, J. M., & Gillis, J. A. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.31.535112 · Cited by 7 · see citing works
Aderibigbe, O., Wood, L. B., & Margulies, S. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083531 · Cited by 6 · see citing works
“KCNV2 is known as a marker for severe epilepsy [98] and FAM177B is known to be exclusively expressed in microglia [99].”
The Cortical Structural Model Extends to Thalamocortical Connections
Barbas, H., & Zikopoulos, B. (2025) · European Journal of Neuroscience · doi:10.1111/ejn.70167 · Cited by 6 · see citing works
Species-specific chromatin architecture and neurogenesis mediated by a human enhancer
Mosti, F., Liu, J., Lam, K., Dillon, N. R., Skavicus, S., Kapps, V. A., Gjoni, K., Lee, C.-F., Glidewell, E. N., Heaton, N. S., et al. (2026) · Cell stem cell · doi:10.1016/j.stem.2026.02.009 · Cited by 6 · see citing works
Inflammation molecular network alterations in a depressive-like primate model
Bu, S., Wang, Q., Zhang, G., Zhang, Z., Dai, J., & Zhang, Z. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.03.021 · Cited by 5 · see citing works
The Placental Steroid Hypothesis of Human Brain Evolution
Tsompanidis, A., Burton, G. J., Baron‐Cohen, S., & Dunbar, R. (2025) · Evolutionary Anthropology Issues News and Reviews · doi:10.1002/evan.70003 · Cited by 4 · see citing works
“Increased spine number and glial cell specialisation have recently been shown to be a characteristic feature of human neurons compared to other primates [66 – 68].”
Co-Conservation of synaptic gene expression and circuitry in collicular neurons
Liu, Y., McDaniel, J. A., Chen, C., Yang, L., Kıpçak, A., Savier, E. L., Erişir, A., Cang, J., & Campbell, J. N. (2025) · Nature Communications · doi:10.1038/s41467-025-64204-5 · Cited by 5 · see citing works
“For instance, neocortical neurons are far more conserved across species than neocortical glia 61 – 63 .”
Shaping the Neocortex: Radial Glia and Astrocytes in Development and Evolution
Mosti, F., Kawasaki, H., Babbitt, C. C., Benedetto, B. D., Silver, D. L., Kalebic, N., & Falcone, C. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1301-25.2025 · Cited by 5 · see citing works
Walsh, J. T., Junker, I. P., Chen, Y., Chen, Y., Gifford, H., Chen, D. S., & Ding, Y. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2516083122 · Cited by 5 · see citing works
Human CLOCK enhances neocortical function
Liu, Y., Fontenot, M. R., Kulkarni, A., Khandelwal, N., Park, S. H. E., Criswell, C. J., Harper, M. J., Xu, P., Gupta, N., Gibson, J. R., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-01993-4 · Cited by 10 · see citing works
“The transcription factor CLOCK (or circadian locomotor output cycles kaput) has significantly increased human-specific expression in the cerebral cortex compared to nonhuman primates and mouse 7,24–30 (Extended Data Fig.”
RNA-programmable cell-type monitoring and manipulation in the human cortex with CellREADR
Matthews, E. A., Russ, J. B., Qian, Y., Zhao, S., Thompson, P., Methani, M., Vestal, M. L., Huang, Z. J., & Southwell, D. G. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116037 · Cited by 5 · see citing works
“62 There is evidence for an increased abundance of CGE interneurons (versus medial ganglionic eminence interneurons) in humans and NHPs as compared to mice, 3,7,9 with some studies suggesting specific expansion of CALB2 populations.”
He, S., Zhang, X., & Zhu, H. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00659-3 · Cited by 5 · see citing works
“…lncRNAs are key regulators of genomic imprinting and complex genomic imprinting occurs in the brain) [10, 11, 13, 14, 64]; the latter is supported by findings that gene expression in immune-related microglia, astrocytes, and oligodendrocytes shows more cross-species divergence than in neurons [59].”
BackgroundResultInfluentialInter-individual variation in human cortical cell type abundance and expressionPreprint
Johansen, N., Somasundaram, S., Travaglini, K. J., Yanny, A. M., Shumyatcher, M., Casper, T., Cobbs, C., Dee, N., Ellenbogen, R. G., Ferreira, M. L., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.10.07.511366 · Cited by 5 · see citing works
The molecular and cellular underpinnings of human brain lateralizationPreprint
Labache, L., Chopra, S., Zhang, X.-H., & Holmes, A. J. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.11.648388 · Cited by 5 · see citing works
“As described by Zhang and colleagues 33 , these 24 cellular classes exhibit distinct laminar specializations, developmental origins, morphologies, spiking patterns, and broad projection targets 61 .”
CellMemory: hierarchical interpretation of out-of-distribution cells using bottlenecked transformer
Wang, Q., Zhu, H., Hu, Y., Chen, Y., Wang, Y., Li, G., Li, Y., Chen, J., Zhang, X., Zou, J., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03638-y · Cited by 8 · see citing works
Osugi, T., Shiraishi, A., Sasakura, Y., Sugahara, K., Yamagaki, T., Yamamoto, T., & Satake, H. (2025) · iScience · doi:10.1016/j.isci.2025.113413 · Cited by 4 · see citing works
Zhang, X., Liu, Q., Liu, C., Wang, Z., Fu, K., Lan, C., Xu, T., Zhou, X., Kendrick, K. M., Yao, D., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2520651122 · Cited by 4 · see citing works
Unique and divergent features of human brain development
Salamon, I., Doyle, D. Z., Bandler, R. C., Pattabiraman, K., & Šestan, N. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103133 · Cited by 5 · see citing works
Bakos, E., Tiszlavicz, Á., Szegedi, V., Douida, A., Furdan, S., Welter, D. K., Landry, J. J. M., Bende, B., Hutóczki, G., Barzó, P., et al. (2025) · PLoS Biology · doi:10.1371/journal.pbio.3003549 · Cited by 4 · see citing works
Tandem repeats in human brain evolution and disease susceptibility
Lee, H., & An, J. (2026) · Molecules and Cells · doi:10.1016/j.mocell.2026.100363 · Cited by 4 · see citing works
Genetic Animal Models of Idiopathic Generalized Epilepsies: What Can We Learn from Them?
Lakaye, B., & Nguyen, L. (2025) · Biomedicines · doi:10.3390/biomedicines13061301 · Cited by 4 · see citing works
“As an example, three glutamate AMPA receptor subunits are expressed at more than threefold higher levels in human astrocytes, indicating an enhanced responsiveness of these cells to glutamate [270].”
Organizational Principles of the Primate Cerebral Cortex at the Single‐Cell Level
Chen, R., Nie, P., Ma, L., & Wang, G. (2025) · Advanced Science · doi:10.1002/advs.202411041 · Cited by 4 · see citing works
Pecoraro, S., Verkerke, M., Sluijs, J. A., Hof, B. V. H., van der Pol, S. M. A., van Strien, M. E., van der Kant, R., de Vries, C. J. M., de Vries, H. E., van de Berg, W. D. J., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.06.017 · Cited by 4 · see citing works
Zambon, M., Mantica, F., Dias, M., Frazer, J., & Irimia, M. (2025) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2025.102387 · Cited by 4 · see citing works
Michielsen, L., Hsu, J., Joglekar, A., Belchikov, N., Reinders, M. J. T., Tilgner, H., & Mahfouz, A. E. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.03.18.585465 · Cited by 4 · see citing works
“Also, the gene expression of human neurons diverged faster from other primates compared to glia 85 .”
BackgroundPal, A., Noble, M. A., Morales, M., Pal, R., Baumgartner, M., Yang, J. W., Yim, K., Uebbing, S., & Noonan, J. P. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.25.600691 · Cited by 4 · see citing works
Selective expansion of motor cortical projections in the evolution of vocal noveltyPreprint
Isko, E. C., Harpole, C. E., Zheng, X. M., Zhan, H., Davis, M. B., Zador, A. M., & Banerjee, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.13.612752 · Cited by 4 · see citing works
“Over long timescales, cortical evolution is likely fueled by changes in the absolute or relative sizes of the cortical fields [15] as well as changes in numbers, composition and spatial distribution of cell-types [16, 17].”
BackgroundHierarchical Interpretation of Out-of-Distribution Cells Using Bottlenecked TransformerPreprint
Wang, Q., Zhu, H., Hu, Y., Chen, Y., Wang, Y., Zhang, X., Zou, J., Kellis, M., Li, Y., Liu, D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.17.628533 · Cited by 4 · see citing works
A consensus spinal cord cell type atlas across mouse, macaque, and humanPreprint
Schmitz, M. T., Johansen, N., Kempynck, N., Kapen, I., Fu, Y., Hewitt, M. N., Seeman, S. C., Kussick, E., Gautier, O., Leone, M. J., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.04.703852 · Cited by 4 · see citing works
“Additionally, comparative studies of primate cortex have established robustly conserved taxonomies 9–11 , demonstrating that widespread cell type conservation underlies core circuit functions with some lineage-specific molecular specializations.”
Cellular and molecular associations with intrinsic brain organization
Feng, G., Chen, J., Jing Sui (Beijing Normal University), my correct affiliation is beijing normal university, N. Q. U. O. S. A. T., & Calhoun, V. D. (2025) · Nature Communications · doi:10.1038/s41467-025-66291-w · Cited by 4 · see citing works
“Together, these fi ndings demonstrate that static and dynamic FNCs provide indirect pathways linking cellular/molecular architecture to cognitive organization, with dynamic FNC offering additional state-speci fi c routes.”
Boroujeni, K. B., Balaram, P., Tiesinga, P. H. E., & Womelsdorf, T. (2025) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2025.102873 · Cited by 4 · see citing works
Subventricular zone radial glial cells maintain inhibitory neuron production in the human brain
Jia, L., Li, X., Yan, Y., Xu, L., Guo, J., Wang, W., Zhang, W., Li, L., Shang, B., Zhang, Y., et al. (2026) · Science · doi:10.1126/science.adw1803 · Cited by 4 · see citing works
Barr, K., & Gilad, Y. (2026) · Genome biology · doi:10.1186/s13059-026-04082-2 · Cited by 3 · see citing works
Human-specific genetic modifiers of cortical architecture and function
Zhao, H., & Schmidt, E. R. E. (2024) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2024.102241 · Cited by 3 · see citing works
Progress in biomedical engineering during 2023 in China
Yu, Z., Song, Z., Xu, H., Wang, J., Wang, C., & Zhao, G. (2024) · EngMedicine · doi:10.1016/j.engmed.2024.100039 · Cited by 3 · see citing works
Evolution of neuroglia: From worm to man
Pękowska, A., Verkhratsky, A., & Falcone, C. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19104-6.00004-8 · Cited by 3 · see citing works
Decoding human brain evolution: Insights from genomics
Liu, Y., Li, M., Segal, A., Zhang, M., & Šestan, N. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103033 · Cited by 3 · see citing works
Single-cell multiomic human brain atlas reveals regulatory drivers of cortical regionality
Palmer, C. R., Song, J., Yang, B., Chen, C.-J., Diep, D. H., Conklin, K. Y., Plongthongkum, N., Indralingam, H. S., Liu, C. S., Kurtz, J. S., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-69368-2 · Cited by 3 · see citing works
Uribe‐Salazar, J. M., Kaya, G., Weyenberg, K., Radke, B., Hino, K., Soto, D. C., Shiu, J.-L., Zhang, W., Ingamells, C., Haghani, N. K., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.11.612570 · Cited by 3 · see citing works
MerQuaCo: a computational tool for quality control in image-based spatial transcriptomicsPreprint
Martin, N. X., Olsen, P. A., Quon, J., Campos, J., Cuevas, N. V., Nagra, J., VanNess, M., Maltzer, Z., Gelfand, E. C., Oyama, A. A., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.04.626766 · Cited by 3 · see citing works
What makes human cortical pyramidal neurons functionally complexPreprint
Aizenbud, I., Yoeli, D., Beniaguev, D., de Kock, C. P. J., London, M., & Segev, I. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.12.17.628883 · Cited by 3 · see citing works
- Authors
- 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., Seeman, S. C., Travaglini, K. J., Basu, S., Beaudin, M., Bertagnolli, D., Crow, M., Ding, S.-L., Eggermont, J., Glandon, A., Goldy, J., Kiick, K., Kroes, T., McMillen, D., Pham, T., Rimorin, C., Siletti, K., Somasundaram, S., Tieu, M., Torkelson, A., Feng, G., Hopkins, W. D., Höllt, T., Keene, C. D., Linnarsson, S., McCarroll, S. A., Lelieveldt, B. P., Sherwood, C. C., Smith, K., Walsh, C. A., Dobin, A., Gillis, J., Lein, E. S., Hodge, R. D., & Bakken, T. E.
- Affiliations
- Allen Institute for Brain Science (US)
- Boston Children's Hospital (US)
- Cold Spring Harbor Laboratory (US)
- Harvard University (US)
- Leiden University Medical Center (NL)
- Karolinska Institutet (SE)
- Broad Institute (US)
- The University of Texas MD Anderson Cancer Center (US)
- Delft University of Technology (NL)
- University of Washington (US)
- George Washington University (US)
- University of Toronto (CA)
- Corresponding author
- Jorstad, Nikolas L.
- Song, Janet H. T.
- Exposito-Alonso, David
- Hodge, Rebecca D.
- Bakken, Trygve E.
- ORCID
- Jorstad, Nikolas L.
- Song, Janet H. T.
- Exposito-Alonso, David
- Suresh, Hamsini
- Castro-Pacheco, Nathan
- Krienen, Fenna M.
- Yanny, Anna Marie
- Close, Jennie
- Gelfand, Emily
- Long, Brian
- Seeman, Stephanie C.
- Travaglini, Kyle J.
- Basu, Soumyadeep
- Beaudin, Marc
- Bertagnolli, Darren
- Crow, Megan
- Ding, Song-Lin
- Eggermont, Jeroen
- Glandon, Alexandra
- Goldy, Jeff
- Kiick, Katelyn
- Kroes, Thomas
- McMillen, Delissa
- Pham, Trangthanh
- Rimorin, Christine
- Siletti, Kimberly
- Somasundaram, Saroja
- Tieu, Michael
- Torkelson, Amy
- Feng, Guoping
- Hopkins, William D.
- Höllt, Thomas
- Keene, C. Dirk
- Linnarsson, Sten
- McCarroll, Steven A.
- Lelieveldt, Boudewijn P.
- Sherwood, Chet C.
- Smith, Kimberly
- Walsh, Christopher A.
- Dobin, Alexander
- Gillis, Jesse
- Lein, Ed S.
- Hodge, Rebecca D.
- Bakken, Trygve E.
- Venue
- Science
- Published
- 2023-10-13
- Volume
- 382
- Issue
- 6667
- Pages
- eade9516-eade9516
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC10659116
- OpenAlex
- W4387595270
- Cited by
- 208
- References
- 89
- Citations by year
- 2026: 58 · 2025: 77 · 2024: 57 · 2023: 15 · 2022: 1
- FWCI
- 18.48
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Research Repository (Delft University of Technology) (submittedVersion)
- Funders
- National Science Foundation (NS092988, U01MH114819, 2021785)
- Nancy and Buster Alvord Endowment
- National Alliance for Research on Schizophrenia and Depression
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (024.004.012, 17126, BRAINSCAPES 024.004.012)
- National Institutes of Health (5u01mh114812-03, 1f32mh114501-01, EF-2021785, U01MH114812)
- Genentech
- National Institute of Mental Health (U19MH114821, U01MH114812, U01MH114819, R01MH113005, F32-MH114501, U19MH114830)
- National Human Genome Research Institute (R01HG011641, R01HG009318)
- National Institute of Neurological Disorders and Stroke (R24NS092988)
- U.S. National Library of Medicine (R01LM012736)
- Division of Emerging Frontiers
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD105351)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
- Keywords
- middle temporal gyrus, neocortex evolution, single-nucleus transcriptomics, cell type composition, laminar organization, deep-layer neurons, microglia, astrocytes, oligodendrocytes, oligodendrocyte precursor cells, chimpanzees, gorillas, rhesus monkeys, marmoset, primate brain evolution
- MeSH terms
- Animals, Pan troglodytes, Cognition, Gorilla gorilla, Humans, Macaca mulatta, Phylogeny, Species Specificity, Temporal Lobe, Hominidae, Neocortex, Gene Expression Profiling, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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