Epigenomic cell-type classification and regulatory element identification in the human brain
This project takes a team approach to generate single nuclei DNA cytosine methylation profiles (snmC-seq3, Ecker and Behrens labs) and chromatin accessibility maps (snATAC-seq, Ren and Behrens labs) of cells isolated from 41 anatomically defined regions of the human brain. This effort is a collaboration with the laboratory of Ed Lein (U01MH114812), who is developing single cell transcriptomic data from these same matched tissues, pooled from three donor brains. Upon completion, we will generate genomic mC DNA sequences from at least 110,700 neurons and 12,300 glial cells, as well as chromatin accessibility profiles from at least 410,000 brain cells. Multi-modal integration of these data sets with matched RNA transcriptomic data from the Lein group will identify consensus cell types and associated gene regulatory elements in these 41 tissue areas. Cell type-specific markers predicted through this bioinformatics analysis will be validated through RNA in situ hybridization and immunohistochemistry analysis. These efforts will support the future development of molecular tools to target specific human brain cell types, tools that will enhance the understanding normal brain function and support the discovery of targeted therapeutic approaches to treat human disease.
Project Leadership
Joseph Ecker, Ph.D. (Multiple Principal Investigator)
Howard Hughes Medical Institute Investigator, Professor and Director, Genomic Analysis Laboratory
Salk Institute for Biological Studies
https://www.salk.edu/scientist/joseph-ecker/
Margarita Behrens, Ph.D. (Multiple Principal Investigator)
Research Professor, Computational Neurobiology Laboratory
Salk Institute for Biological Studies
https://www.salk.edu/scientist/margaritabehrens/
Bing Ren, Ph.D. (Co-Investigator)
Professor, Cellular and Molecular Medicine, Ludwig Cancer Research Institute
University of California, San Diego
http://renlab.sdsc.edu/renlab_website/
Ed Lein, Ph.D. (Collaborator)
Investigator
Allen Institute for Brain Science, Seattle, Washington, USA
https://www.alleninstitute.org/what-we-do/brain-science/about/team/staff-profiles/ed-lein/
Project Data Types
- DNA methylation profiling of neurons in human brain regions using single-nuclei methylC-Seq (snmC-seq)
- Chromatin accessibility profiling in human brain cells using single-nuclei ATAC-Seq (snATAC-seq)