Comprehensive Single-Cell Multi-Omic Atlas of Adult Rhesus Macaque Brain

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Summary

Utilizing the primate brain's complex cellular structure is essential to grasp human cognition, behavior, and ailments. In their study, they crafted a detailed molecular map of the rhesus macaque brain, examining millions of transcriptomes and epigenomes from individual nuclei in 30 distinct brain areas. These analyses showed varying cell compositions in different regions, signifying their unique functional roles. They also pinpointed over a million potential regulatory elements, many being new discoveries. These findings help demystify the genetic control mechanisms and disease susceptibility in specific cell types, offering a foundation for understanding human brain evolution and potential disease solutions.

Research Criteria

The study sought to detail the varied cell structures in the primate brain, crucial for comprehending human cognition, behavior, and illness. They produced a comprehensive molecular map of the rhesus macaque brain, encompassing both transcriptomes and epigenomes. This extensive profiling captured data from millions of individual nuclei sourced from various regions of the mature brain.

Fig.1 Experimental design¹.

Sample Type

They sourced specimens from individual nuclei in 30 distinct areas of an adult rhesus macaque's brain for their cellular analyses.

Result—A Molecular Classification of Cell Types in the Monkey Brain

In this study encompassing the primate brain, researchers meticulously profiled single-nucleus RNA sequences from 30 distinct brain regions, employing the sophisticated sci-RNA-seq3 technique. This endeavor yielded a staggering 2,583,967 nuclei transcriptome profiles, post stringent quality control measures. Through this data, they discerned 17 molecularly unique cell types, or "cell classes," which encompassed both neuronal and non-neuronal cells. Notably, this taxonomy revealed previously unidentified neuron-like populations and a microglia-like group. The study's breadth allowed for a comprehensive cellular composition analysis across these regions, unveiling the dominance of glutamatergic neurons in the cortex and cerebellar neurons in the cerebellum. Conversely, the subcortex and brainstem presented a more diverse cellular makeup. The research also spotlighted the relatively rare dopaminergic and serotonergic neurons, underscoring their pivotal roles in processes like voluntary movement, mood regulation, and their association with disorders like Parkinson's and depression.

Fig.2 Macaque brain atlas snRNA-seq dataset summary¹.

Result—Joint Transcriptome and Epigenomic Analysis of Single-Nucleus Data

Researchers conducted a comprehensive analysis of single-nucleus transcriptomic and epigenomic data to delve into the key regulatory genomic regions within brain cells. By employing three-level single-cell combinatorial indexing ATAC-seq (sci-ATAC-seq3) and single-nucleus assay for transposase-accessible chromatin with sequencing (snATAC-seq), they meticulously profiled epigenomes across diverse brain regions. To ensure data consistency, age-, sex-, and hemisphere-matched tissue samples were utilized. The data underwent uniform manifold approximation and projection (UMAP) and Leiden clustering for batch correction. Integration of these datasets was achieved using the graph-linked unified embedding (GLUE) approach, revealing insights into various brain cell classes. The findings, showcased in the Macaque Brain Atlas sci-ATAC-seq dataset, highlighted the alignment between snATAC-seq and snRNA-seq data, validating the robustness of the homogenization and nuclei isolation methods used in their research.

Fig.3 The macaque brain atlas sci-ATAC-seq dataset was created, and cell classifications were identified¹.

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Single Nuclei RNA Sequencing Service

At Creative Biolabs, we offer customized, top-tier single-cell nucleus RNA sequencing services, empowering worldwide biomedical research initiatives. Our dedicated platform is expertly designed for comprehensive tissue analysis, including brain, heart, kidney, and unique cryopreserved samples. This advanced technology simplifies the study of tumor cell diversity and the understanding of disease pathways.

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Single Cell ATAC Service

At Creative Biolabs, we take great pride in providing a wide range of meticulously customized, high-quality services for single cell ATAC profiling, addressing a variety of scientific inquiries worldwide. Our expertise in deciphering chromatin accessibility at the cellular level reveals profound insights into the intricate mechanisms that govern these processes.

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At Creative Biolabs, we take pride in being a leading provider of cutting-edge single-cell analytical solutions. Our dedicated team of seasoned scientists harnesses a range of advanced technologies to deliver high-quality data and insights to researchers and institutions worldwide. With our single nuclei RNA sequencing service, we offer in-depth analysis of gene expression at the single nuclei level, providing a detailed understanding of cellular heterogeneity and function. Additionally, our single-cell ATAC sequencing service offers a comprehensive view of chromatin accessibility within individual cells, aiding in the identification of regulatory elements and the elucidation of cellular states for diverse applications in fundamental research, pharmaceutical innovation, and diagnostic advancement.

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Reference

1. Chiou, Kenneth L et al. "A single-cell multi-omic atlas spanning the adult rhesus macaque brain." Science advances vol. 9,41 (2023): eadh1914.