U01 - Zhang, Kun 1U01MH114828-01A1

Toward a Human Adult Brain Cell Atlas with Single-Cell Technologies

Understanding the functional diversity of the adult human brain requires a full molecular characterization of brain cell types. To achieve this goal, the “Center for Accessibility and Transcriptomics in the Human Adult Brain” (CATHAB) will focus on: 1) Collection and standardization of human brain samples by integrating magnetic resonance imaging (MRI), histology, and preparatory procedures to reduce post-mortem interval (PMI) and optimize multi-omic data integrity; 2) Assessment of selected brains by three highly multiplexed single-cell technologies to produce transcriptome, accessibility, and spatial data at single-cell resolution; 3) Development and application of novel computational approaches for scalable and efficient integration and analysis of multi-omic data that will encompass all cell types in the brain; 4) Spatial mapping of the molecular cell types that will extend to major Brodmann Areas (BAs) of the cerebral cortex as well as subdivisions of adult brain.  Data generated in this approach will be combined and integrated with analyses by other groups in the BICCN.  

  • The Center will identify and characterize cell types across the human brain. More than 2 million cells across 44 BAs and 16 subcortical regions will be subjected to single-cell transcriptome and chromatin accessibility profiling.
  • A highly multiplexed RNA in situ mapping method (DART-FISH) will be implemented to characterize spatial relationships among identified cell types.
  • Computational approaches will be developed to generate a working multi-omic atlas essential for future investigations into cell type specific differences across neurological disease states.

Project Leadership

Kun Zhang, Ph.D. (Principal Investigator)
Professor of Bioengineering
Institute for Genomic Medicine
University of California San Diego
http://genome-tech.ucsd.edu/ZhangLab/


Jerold Chun, M.D., Ph.D. (Principal Investigator)
Professor, Degenerative Diseases Program
Senior Vice President, Drug Discovery
Neuroscience and Aging Center
Sanford Burnham Prebys Medical Discovery Institute
http://labs.sbpdiscovery.org/centerandlabs/neuroagingstem/chunlab/


Peter Kharchenko, Ph.D. (Principal Investigator)
Associate Professor
Department of Biomedical Informatics
Harvard Medical School
http://pklab.med.harvard.edu/


Blue B. Lake, Ph.D. (Project Scientist)
Department of Bioengineering
University of California San Diego
http://genome-tech.ucsd.edu/ZhangLab/


Benjamin Siddoway, Ph.D. (Research Specialist)
Neuroscience and Aging Center
Sanford Burnham Prebys Medical Discovery Institute
http://labs.sbpdiscovery.org/centerandlabs/neuroagingstem/chunlab/

 

 


Project Data Types

  • Transcriptomic profiling of individual cells from human brain regions using single-nucleus RNA-seq

  • Chromatin accessibility profiling of individual cells from human brain regions using single-nucleus THS-Seq 

  • Matched spatial information with multi-omics data via DART-FISH


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