U19 - Ecker 1U19MH114831-01

Center for Epigenomics of the Mouse Brain Atlas

A comprehensive understanding of how neural circuits spanning the entire brain generate the full repertoire of perception and behaviors requires a list of brain cell types, as well the means to target each cell type, to interrogate the functional interactions that give rise to the emergent properties of the whole system. To address these challenges, the “Center for Epigenomics of the Mouse Brain Atlas” (CEMBA) will focus on “epigenetic profiling”, for identification, cataloging, characterization and genetic targeting of mammalian brain cell types. This approach is complementary to RNA expression analysis employed by other groups in the BICCN.  

  • The Center will identify and characterize cell types across the mouse central nervous system. More than 1 million single neurons across the whole brain will be subjected to single cell epigenetic profiling, including DNA methylation analysis (single nuclear methyl Cytosine sequencing, snmC-seq) and chromatin accessibility (single nucleus Assay for Transposase-Accessible Chromatin, snATAC-seq).
  • Using viral vectors for the identification and isolation of transsynaptic partners, cell types emerging from these profiles will be linked to anatomy for detailed characterization of their locations, morphology, and brain-wide connectivity and projections.
  • By focusing on epigenetic profiling, the Center will harness knowledge of gene regulatory mechanisms to identify cell-type specific genetic enhancers. Knowledge of differences in the connectivity/anatomy of cell types will be used to allow epigenetic profiles to be linked to anatomy
  • Knowledge of epigenetic differences between cell populations will be used to identify enhancers, which restrict gene expression to neuronal populations that will be subsequently subjected to detailed characterization.

Project Leadership

Joseph Ecker, Howard Hughes Medical Institute Investigator, Professor and Director, Genomic Analysis Laboratory, Salk Institute for Biological Studies (Principal Investigator) 
https://www.salk.edu/scientist/joseph-ecker/ 

 

Edward Callaway, Professor, Systems Neurobiology Laboratory, Salk Institute for Biological Studies (Principal Investigator) 
https://www.salk.edu/scientist/edward-callaway/ 

 

Margarita Behrens, Research Professor, Computational Neurobiology Laboratory, Salk Institute for Biological Studies  
https://www.salk.edu/scientist/margaritabehrens/

 

Hong Wei Dong, Professor of Neurology, Laboratory of Neuro Imaging, Keck School of Medicine, University of Southern California 
http://donglab.loni.usc.edu/

 

Eran Mukamel, Assistant Professor, Cognitive Sciences, University of California, San Diego 
http://www.cogsci.ucsd.edu/people/faculty/eran-mukamel.html

 

Xin Jin, Associate Professor, Molecular Neurobiology Laboratory, Salk Institute for Biological Studies 
https://www.salk.edu/scientist/xin-jin/

 

Kuo-Fen Lee, Professor, Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies  
https://www.salk.edu/scientist/kuo-fen-lee/

 

Bing Ren, Professor, Cellular and Molecular Medicine, Ludwig Cancer Research Institute, University of California, San Diego 
http://renlab.sdsc.edu/renlab_website/
 


Project Data Types

  • DNA methylation profiling of neurons in mouse brain regions using single-nuclei methylC-Seq (snmC-seq) 
  • Chromatin accessibility profiling in mouse brain cells using single-nuclei ATAC-Seq (snATAC-seq) 
  • Matched anatomical connectivity information by viral tracing and microscopy 

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