Single cell transcriptional and epigenomic atlas of the macaque brain across the lifespan
New technologies are enabling molecular profiling of single brain cells at remarkable throughput. However, these new methods have yet to be extensively applied to the brains of model organisms that bridge the evolutionary distance between mouse and human, including the most common nonhuman primate model system - the rhesus macaque. This project will generate an anatomically resolved, single cell atlas of the epigenome (5.5 million cells) and transcriptome (11 million cells) of the rhesus macaque brain. The PIs will use two recently developed methods that rely on combinatorial indexing to cost-effectively profile the epigenomes (sci-ATAC-seq) and transcriptomes (sci-RNA-seq) of large numbers of cells. In aim 1 the team will generate high resolution, single cell epigenetic and transcriptional atlases of one male and one female rhesus macaque brain by profiling chromatin accessibility in 750,000 nuclei (sci-ATAC-seq) and transcription in 1,500,000 nuclei (sci-RNA-seq) from each of two macaque brains (for a total of 4.5 million cells). These will be obtained from 25 anatomically dissected brain regions (30,000 sci-ATAC-seq and 60,000 sci-RNA-seq profiles per region per brain). In the second aim, the team will extend these atlases to span the primate lifespan by performing single cell epigenetic and transcriptional profiling of the brains of 50 additional rhesus macaques (25 regions per brain; 3,200 sci-ATAC-seq and 6,400 sci-RNA-seq profiles per individual/region, for a total of 12 million molecularly profiled cells). This large sample size will characterize natural variation in chromatin accessibility and transcription within each cell type, between individuals, sexes, and across the natural lifespan of rhesus macaques. At 16.5 million cells, this rhesus macaque brain atlas will comprise the largest transcriptional and epigenomic single cell dataset of any primate organ to date. It will therefore be an essential resource, complementary to other efforts, for identifying the distribution and function of key cell types across the primate brain, allowing for the development of cell type- and region-specific molecular interventions that will help to understand brain function and the etiology, and potentially the treatment, of brain disorders.
Project Leadership
Noah Snyder-Mackler, Ph.D. (Multiple Principal Investigator)
Assistant Professor, Center for Evolution and Medicine, School of Life Sciences
Arizona State University
https://smack-lab.com/
Michael Platt, Ph.D. (Multiple Principal Investigator)
Professor, Neuroscience, Psychology, & Marketing
University of Pennsylvania
http://plattlabs.rocks
Jay Shendure, M.D. Ph.D. (Multiple Principal Investigator)
Professor, Genome Sciences
University of Washington
https://shendure-web.gs.washington.edu
Project Data Types
- 3 million sci-RNA-seq libraries across 25 regions from one adult male and one adult female rhesus macaque: 60,000 nuclei per region per brain.
- 1.5 million sci-ATAC-seq libraries across 25 regions from one adult male and one adult female rhesus macaque: 30,000 nuclei per region per brain.
- 8 million sci-RNA-seq libraries across 25 regions from 25 males and 25 females across the macaque lifespan: 6,400 sci-RNA-seq profiles per individual per brain
- 4 million sci-RNA-seq libraries across 25 regions from 25 males and 25 females across the macaque lifespan: 3,200 sci-ATAC-seq profiles per individual per brain
Related Resources
- Snyder-Mackler Laboratory: https://smack-lab.com/
- Platt Laboratory: http://plattlabs.rocks
- Shendure Laboratory: https://shendure-web.gs.washington.edu