Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains
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Abstract
Identification of gene expression traits unique to the human brain sheds light on the molecular mechanisms underlying human evolution. Here, we searched for uniquely human gene expression traits by analyzing 422 brain samples from humans, chimpanzees, bonobos, and macaques representing 33 anatomical regions, as well as 88,047 cell nuclei composing three of these regions. Among 33 regions, cerebral cortex areas, hypothalamus, and cerebellar gray and white matter evolved rapidly in humans. At the cellular level, astrocytes and oligodendrocyte progenitors displayed more differences in the human evolutionary lineage than the neurons. Comparison of the bulk tissue and single-nuclei sequencing revealed that conventional RNA sequencing did not detect up to two-thirds of cell-type-specific evolutionary differences.
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Using snRNA-seq in AC and CN, NPAS3 shows higher expression in humans compared to chimpanzee astrocytes in the two telencephalic regions analyzed.
“However, when using snRNA-seq in three brain regions (anterior cingulate cortex, AC; Caudate Nucleus, CN and cerebellar gray matter, CB), NPAS3 show higher expression in humans compared to chimpanzee astrocytes in the two telencephalic regions analyzed, AC and CN (Khrameeva et al. 2020).”
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 Khrameeva et al. 2020
The Results section (Single-nuclei transcriptome analysis; page not provided) confirms that the study used snRNA-seq in AC, CN, and CB. The Results section on immunohistochemistry reports higher expression of MSI2 and NFAT5 in human AC astrocytes, but the passages found for NPAS3 do not establish higher NPAS3 expression in human than chimpanzee astrocytes in both AC and CN. (LLM, conf=0.85)
Experimental — accuracy not yet measuredNPAS3 is differentially expressed in various cell types such as inhibitory neurons and astrocytes during development (human vs macaque) and also in adults (human vs chimpanzee/macaque).
“Comparative analysis of available transcriptomic data of human and non-human primates (chimpanzee and macaque [Sousa et al. 2017; Pollen et al. 2019; Khrameeva et al. 2020; Jorstad et al. 2023]) indicates that NPAS3 is differentially expressed in various cell types such as inhibitory neurons and astrocytes during development (human vs macaque) and also in adults (human vs. chimpanzee/macaque).”
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 Khrameeva et al. 2020
The Results sections on cell-type-based expression evolution and snRNA-seq report human–nonhuman primate expression differences in astrocytes and inhibitory neurons, but do not identify NPAS3 as one of the genes. A search for NPAS3 and for the claimed developmental and adult comparisons found no passage establishing those NPAS3-specific findings. (LLM, conf=0.75)
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References 65 · Cited by 162
- Authors
- Khrameeva, E., Kurochkin, I., Han, D., Guijarro, P., Kanton, S., Santel, M., Qian, Z., Rong, S., Mazin, P., Sabirov, M., Bulat, M., Efimova, O., Tkachev, A., Guo, S., Sherwood, C. C., Camp, J. G., Pääbo, S., Treutlein, B., & Khaitovich, P.
- Affiliations
- Skolkovo Institute of Science and Technology (RU)
- Guangzhou Women and Children Medical Center (CN)
- Chinese Academy of Sciences (CN)
- Max Planck Institute for Evolutionary Anthropology (DE)
- Russian Academy of Sciences (RU)
- George Washington University (US)
- Institute of Molecular and Clinical Ophthalmology Basel (CH)
- ETH Zurich (CH)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2020-05
- Volume
- 30
- Issue
- 5
- Pages
- 776-789
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC7263190
- OpenAlex
- W3026796704
- Cited by
- 162
- References
- 65
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 25 · 2023: 26 · 2022: 25 · 2021: 26 · 2020: 8 · 2019: 2
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Russian Foundation for Basic Research (20-34-70077)
- Chinese Academy of Sciences (XDB13010200)
- National Natural Science Foundation of China (31420103920)
- National One Thousand Foreign Experts Plan (WQ20123100078)
- the National Key R&D Program of China (2017YFA0505700)
- the Russian Science Foundation (16-14-00220)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- human brain evolution, single-nucleus transcriptomics, gene expression evolution, chimpanzees, bonobos, macaque, cerebral cortex, hypothalamus, cerebellum, astrocytes, oligodendrocyte progenitors, cell type-specific gene expression, single-cell resolution
- MeSH terms
- RNA-Seq, Animals, Brain, Pan troglodytes, Humans, Immunohistochemistry, Macaca, Neurons, Evolution, Molecular, Pan paniscus, Single-Cell Analysis, Transcriptome
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