Transcriptomic diversity of cell types across the adult human brain
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Abstract
The human brain directs complex behaviors, ranging from fine motor skills to abstract intelligence, but the diversity of cell types that support these skills has not been fully described. In this work, we used single-nucleus RNA sequencing to systematically survey cells across the entire adult human brain. We sampled more than three million nuclei from approximately 100 dissections across the forebrain, midbrain, and hindbrain in three postmortem donors. Our analysis identified 461 clusters and 3313 subclusters organized largely according to developmental origins and revealing high diversity in midbrain and hindbrain neurons. Astrocytes and oligodendrocyte-lineage cells also exhibited regional diversity at multiple scales. The transcriptomic census of the entire human brain presented in this work provides a resource for understanding the molecular diversity of the human brain in health and disease.
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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 [19]
The paper’s main text (page unavailable) describes its cell-type classification as a foundation for exploring brain circuitry and implications for human health. The Data and materials availability section identifies the data as BICCN data. Neither passage establishes BICAN classifications or specifically supports understanding the epigenomic underpinnings of Alzheimer’s disease. (LLM, conf=0.85)
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 [19]
The Methods describe screening postmortem brains for RNA quality and freezing and storing the tissue; the main text reports high-quality samples used for single-nucleus RNA sequencing. Our copy does not give a mean postmortem interval of 7.0 hours or establish that these methods enabled exceptionally high-quality snATAC-seq and MERFISH profiling. Page numbers were not available in the indexed passages. (LLM, conf=0.87)
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BackgroundMethodInfluentialA high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain
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- Authors
- Siletti, K., Hodge, R., Mossi Albiach, A., Lee, K. W., Ding, S.-L., Hu, L., Lönnerberg, P., Bakken, T., Casper, T., Clark, M., Dee, N., Gloe, J., Hirschstein, D., Shapovalova, N. V., Keene, C. D., Nyhus, J., Tung, H., Yanny, A. M., Arenas, E., Lein, E. S., & Linnarsson, S.
- Affiliations
- Karolinska Institutet (SE)
- Allen Institute for Brain Science (US)
- Karolinska Institute, 171 77 Stockholm, Sweden.
- University of Washington (US)
- Corresponding author
- Siletti, Kimberly
- Hodge, Rebecca
- Linnarsson, Sten
- ORCID
- Siletti, Kimberly
- Hodge, Rebecca
- Mossi Albiach, Alejandro
- Lee, Ka Wai
- Ding, Song-Lin
- Hu, Lijuan
- Lönnerberg, Peter
- Bakken, Trygve
- Casper, Tamara
- Clark, Michael
- Dee, Nick
- Gloe, Jessica
- Hirschstein, Daniel
- Shapovalova, Nadiya V.
- Keene, C. Dirk
- Nyhus, Julie
- Tung, Herman
- Yanny, Anna Marie
- Arenas, Ernest
- Lein, Ed S.
- Linnarsson, Sten
- Venue
- Science
- Published
- 2023-10-13
- Volume
- 382
- Issue
- 6667
- Pages
- eadd7046-eadd7046
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4387568450
- Cited by
- 832
- References
- 9
- Citations by year
- 2026: 288 · 2025: 330 · 2024: 163 · 2023: 48 · 2022: 3
- FWCI
- 74.05
- 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)
- Funders
- Torsten Söderbergs Stiftelse
- European Commission (H2020, 884608, 874758)
- Stiftelsen för Strategisk Forskning (SB16-0065)
- Hjärnfonden
- Karolinska Institutet (2020-01426)
- Knut och Alice Wallenbergs Stiftelse (2018.0220, 2018.0172, 2015.0041)
- Vetenskapsrådet (2018-)
- Science for Life Laboratory
- National Institutes of Health (H2020, MH114812-02)
- Horizon 2020 Framework Programme (874758)
- Uppsala Multidisciplinary Center for Advanced Computational Science
- 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 Chromatin Dynamics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- single-nucleus RNA sequencing, transcriptomic diversity, neuronal cell types, astrocytes, oligodendrocyte lineage, developmental origins, midbrain, hindbrain, forebrain, postmortem brain, cell type atlas
- MeSH terms
- Single-Cell Gene Expression Analysis, Adult, Brain, Humans, Mesencephalon, Neurons, Prosencephalon, Gene Expression Profiling, Transcriptome
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