A Single-cell Multi-omic Atlas Spanning the Adult Rhesus Macaque Brain

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2023 Oct 12

PMID 37824616

Authors

Kenneth L Chiou

Xingfan Huang

Martin O Bohlen

Sebastien Tremblay

Alex R DeCasien

Diana R ODay

Cailyn H Spurrell

Aishwarya A Gogate

Trisha M Zintel

Madeline G Andrews

Melween I Martinez

Lea M Starita

Michael J Montague

Michael L Platt

Jay Shendure

Noah Snyder-Mackler

Affiliations

Soon will be listed here.

Abstract

Cataloging the diverse cellular architecture of the primate brain is crucial for understanding cognition, behavior, and disease in humans. Here, we generated a brain-wide single-cell multimodal molecular atlas of the rhesus macaque brain. Together, we profiled 2.58 M transcriptomes and 1.59 M epigenomes from single nuclei sampled from 30 regions across the adult brain. Cell composition differed extensively across the brain, revealing cellular signatures of region-specific functions. We also identified 1.19 M candidate regulatory elements, many previously unidentified, allowing us to explore the landscape of cis-regulatory grammar and neurological disease risk in a cell type-specific manner. Altogether, this multi-omic atlas provides an open resource for investigating the evolution of the human brain and identifying novel targets for disease interventions.

Citing Articles

Benchmarking macaque brain gene expression for horizontal and vertical translation.

Luppi A, Liu Z, Hansen J, Cofre R, Niu M, Kuzmin E Sci Adv. 2025; 11(9):eads6967.

PMID: 40020056 PMC: 11870082. DOI: 10.1126/sciadv.ads6967.

Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution.

Yang L, Fang L, Lynch M, Xu C, Hahm H, Zhang Y Sci Adv. 2024; 10(50):eadq6017.

PMID: 39661664 PMC: 11633743. DOI: 10.1126/sciadv.adq6017.

An Honest Reckoning With the Amygdala and Mental Illness.

Fox A, Shackman A Am J Psychiatry. 2024; 181(12):1059-1075.

PMID: 39616453 PMC: 11611071. DOI: 10.1176/appi.ajp.20240941.

The BRAIN initiative: a pioneering program on the precipice.

Miller C, Chen X, Donaldson Z, Marlin B, Tsao D, Williams Z Nat Neurosci. 2024; 27(12):2264-2266.

PMID: 39578571 DOI: 10.1038/s41593-024-01811-3.

Comparative Physiology and Morphology of BLA-Projecting NBM/SI Cholinergic Neurons in Mouse and Macaque.

Luo F, Jiang L, Desai N, Bai L, Watkins G, Eldridge M J Comp Neurol. 2024; 532(11):e70001.

PMID: 39576005 PMC: 11583843. DOI: 10.1002/cne.70001.

References

Gaiano N, Nye J, Fishell G . Radial glial identity is promoted by Notch1 signaling in the murine forebrain. Neuron. 2000; 26(2):395-404. DOI: 10.1016/s0896-6273(00)81172-1. View

Bakken T, Jorstad N, Hu Q, Lake B, Tian W, Kalmbach B . Comparative cellular analysis of motor cortex in human, marmoset and mouse. Nature. 2021; 598(7879):111-119. PMC: 8494640. DOI: 10.1038/s41586-021-03465-8. View

Bakken T, van Velthoven C, Menon V, Hodge R, Yao Z, Nguyen T . Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans. Elife. 2021; 10. PMC: 8412930. DOI: 10.7554/eLife.64875. View

Corces M, Trevino A, Hamilton E, Greenside P, Sinnott-Armstrong N, Vesuna S . An improved ATAC-seq protocol reduces background and enables interrogation of frozen tissues. Nat Methods. 2017; 14(10):959-962. PMC: 5623106. DOI: 10.1038/nmeth.4396. View

Quinlan A, Hall I . BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics. 2010; 26(6):841-2. PMC: 2832824. DOI: 10.1093/bioinformatics/btq033. View

Preuss T . Human brain evolution: from gene discovery to phenotype discovery. Proc Natl Acad Sci U S A. 2012; 109 Suppl 1:10709-16. PMC: 3386880. DOI: 10.1073/pnas.1201894109. View

Navarrete A, van Schaik C, Isler K . Energetics and the evolution of human brain size. Nature. 2011; 480(7375):91-3. DOI: 10.1038/nature10629. View

Kanton S, Boyle M, He Z, Santel M, Weigert A, Sanchis-Calleja F . Organoid single-cell genomic atlas uncovers human-specific features of brain development. Nature. 2019; 574(7778):418-422. DOI: 10.1038/s41586-019-1654-9. View

Allman J, Watson K, Tetreault N, Hakeem A . Intuition and autism: a possible role for Von Economo neurons. Trends Cogn Sci. 2005; 9(8):367-73. DOI: 10.1016/j.tics.2005.06.008. View

10.

Pletscher-Frankild S, Palleja A, Tsafou K, Binder J, Jensen L . DISEASES: text mining and data integration of disease-gene associations. Methods. 2014; 74:83-9. DOI: 10.1016/j.ymeth.2014.11.020. View

11.

Harauz G, Ladizhansky V, Boggs J . Structural polymorphism and multifunctionality of myelin basic protein. Biochemistry. 2009; 48(34):8094-104. DOI: 10.1021/bi901005f. View

12.

Martin B, Qiu C, Nichols E, Phung M, Green-Gladden R, Srivatsan S . Optimized single-nucleus transcriptional profiling by combinatorial indexing. Nat Protoc. 2022; 18(1):188-207. PMC: 9839601. DOI: 10.1038/s41596-022-00752-0. View

13.

Kamma E, Lasisi W, Libner C, Ng H, Plemel J . Central nervous system macrophages in progressive multiple sclerosis: relationship to neurodegeneration and therapeutics. J Neuroinflammation. 2022; 19(1):45. PMC: 8830034. DOI: 10.1186/s12974-022-02408-y. View

14.

Hodge R, Bakken T, Miller J, Smith K, Barkan E, Graybuck L . Conserved cell types with divergent features in human versus mouse cortex. Nature. 2019; 573(7772):61-68. PMC: 6919571. DOI: 10.1038/s41586-019-1506-7. View

15.

Widdig A, Muniz L, Minkner M, Barth Y, Bley S, Ruiz-Lambides A . Low incidence of inbreeding in a long-lived primate population isolated for 75 years. Behav Ecol Sociobiol. 2016; 71(1):18. PMC: 5145906. DOI: 10.1007/s00265-016-2236-6. View

16.

Fakhoury M . Revisiting the Serotonin Hypothesis: Implications for Major Depressive Disorders. Mol Neurobiol. 2015; 53(5):2778-2786. DOI: 10.1007/s12035-015-9152-z. View

17.

Bohlen C, Friedman B, Dejanovic B, Sheng M . Microglia in Brain Development, Homeostasis, and Neurodegeneration. Annu Rev Genet. 2019; 53:263-288. DOI: 10.1146/annurev-genet-112618-043515. View

18.

Hirayama T, Kadooka Y, Tarusawa E, Saitoh S, Nakayama H, Hoshino N . CTCF loss induces giant lamellar bodies in Purkinje cell dendrites. Acta Neuropathol Commun. 2022; 10(1):172. PMC: 9706876. DOI: 10.1186/s40478-022-01478-6. View

19.

Boldog E, Bakken T, Hodge R, Novotny M, Aevermann B, Baka J . Transcriptomic and morphophysiological evidence for a specialized human cortical GABAergic cell type. Nat Neurosci. 2018; 21(9):1185-1195. PMC: 6130849. DOI: 10.1038/s41593-018-0205-2. View

20.

Machlab D, Burger L, Soneson C, Rijli F, Schubeler D, Stadler M . monaLisa: an R/Bioconductor package for identifying regulatory motifs. Bioinformatics. 2022; 38(9):2624-2625. PMC: 9048699. DOI: 10.1093/bioinformatics/btac102. View