U19 - Zeng 1U19MH114830-01

A Comprehensive Whole-brain Atlas of Cell Types in the Mouse

Our goal is to create a high-quality atlas of cell types in the mouse brain by addressing the question: “what is a cell type and how do we define it?”  We will conduct large-scale single-cell transcriptomic analysis across the entire mouse brain, as well as systematic sampling of neuronal morphology and connectivity in a wide range of brain areas. In selected proof-of-principle cases, we will examine the correspondence among the molecular, anatomical, and functional properties of these cells to gain an understanding of how cell types are defined. Finally, we will generate a census of the number and location of cells for each type and develop new genetic tools that target these selected cell types. This research consists of the following major components:  

 

  • A comprehensive whole-brain atlas of transcriptomic cell types in the mouse 
  • An anatomical cell type atlas of gene expression, morphology and connectivity 
  • Functional and multi-modal characterization of cell types in selected circuits 
  • Generation of novel cell type specific mouse genetic tools 
  • Data Core: Centralized data management systems to integrate the diverse data collections 
  • Administrative Core: Collaboration and standardization across groups 

 


Project Leadership

Hongkui Zeng, PhD (Project Director / Principal Investigator) 
Executive Director, Structured Science,  
Allen Institute for Brain Science  
https://www.alleninstitute.org/what-we-do/brain-science/about/team/staff-profiles/hongkui-zeng/ 

 

Lior Pachter, PhD (Multiple Principal Investigator) 
Bren Professor of Computational Biology and Computing and Mathematical Science 
California Institute of Technology
https://bbe.divisions.caltech.edu/people/lior-s-pachter

 

Xiaowei Zhuang, PhD (Multiple Principal Investigator) 
Howard Hughes Medical Institute Investigator 
David B. Arnold Jr. Professor of Science 
Professor of Chemistry and Chemical Biology 
Professor of Physics 
Harvard University  
http://zhuang.harvard.edu/ 

 

Andreas Tolias, PhD (Multiple Principal Investigator) 
Associate Professor, Department of Neuroscience 
Baylor College of Medicine  
https://toliaslab.org/  

 

David J. Anderson, PhD (Multiple Principal Investigator)
Howard Hughes Medical Institute 
Seymour Benzer Professor of Biology 
Director, Tianqiao and Chrissy Chen Institute for Neuroscience 
California Institute of Technology
https://bbe.divisions.caltech.edu/people/david-j-anderson​​​​​​​

 

John Ngai, PhD (Multiple Principal Investigator)
Coates Family Professor of Neurobiology 
Department of Molecular & Cell Biology  
University of California, Berkeley 
https://mcb.berkeley.edu/faculty/all/ngaij 

 

Catherine Dulac, PhD (Co-Investigator)
Higgins Professor of Molecular and Cellular Biology
Lee and Ezpeleta Prfesor of Arts and Sciences
Howard Hughes Medical Institute Investigator
Harvard University
https://www.mcb.harvard.edu/directory/catherine-dulac/

 

Qingming Luo, PhD (Co-Investigator)
Vice President, Huazhong University of Science and Technology (HUST)
Executive Deputy Director, Wuhan National Laboratory for Optoelectronics
Director, The Key Laboratory of Biomedical Photonics of MoE, HUST
MoE Appointed Cheung Kong Professor for Biomedical Photonics, HUST
Founder and Director, Britton Chance Center for Biomedical Photonics, HUST
http://ses.hust.edu.cn/info/1072/1292.htm

 

Rickard Sandberg, PhD (Co-Investigator)
Associate Professor, Department of Cell and Molecular Biology
Karolinska Institutet, Sweden
https://ki.se/en/people/ricsan

 

Philipp Berens, PhD (Co-Investigator)
Full Professor of Data Science for Vision Research
Institute for Ophthalmic Research           
Universität Tübingen, Germany
http://www.eye-tuebingen.de/berens/

 

Davide Risso, PhD (Co-Investigator)
Assistant Professor of Healthcare Policy and Research
Weill Cornell Medical College
http://vivo.med.cornell.edu/display/cwid-dar2062
       

Bosiljka Tasic, PhD (Co-Investigator)
Associate Director, Molecular Genetics
Allen Institute for Brain Science
https://www.alleninstitute.org/what-we-do/brain-science/about/team/staff-profiles/bosiljka-tasic/

 

Julie Harris, PhD (Co-Investigator)
Associate Director, Neuroanatomy
Allen Institute for Brain Science
https://www.alleninstitute.org/what-we-do/brain-science/about/team/staff-profiles/julie-harris/

 

Hanchuan Peng, PhD (Co-Investigator)
Associate Investigator
Allen Institute for Brain Science
https://alleninstitute.org/what-we-do/brain-science/about/team/staff-profiles/hanchuan-peng/

 

Ian Wickersham, PhD (Co-Investigator)
Principal Research Scientist, McGovern Institute for Brain Research
Massachusetts Institute of Technology
http://mcgovern.mit.edu/senior-researchers

 

Jayaram Chandrashekar, PhD (Collaborator)
Project Scientist
Howard Hughes Medical Institute
https://www.janelia.org/people/jayaram-chandrashekar


Project Data Types

  • Large-scale, deep transcriptomic analysis of adult mouse brain-wide structures using SMART-Seq v4 scRNA-seq and snRNA-seq 
  • Large-scale, broad survey of adult mouse brain-wide structures using 10x Genomics Chromium v2 scRNA-seq and snRNA-seq
  • Validation of transcriptomic cell types and marker genes using single-molecule FISH
  • Large-scale, systematic spatial transcriptomic analysis of adult mouse brain-wide structures using MERFISH
  • Triple modality Patch-seq analysis of excitatory and inhibitory neurons in targeted adult mouse cortical and subcortical structures by integrating electrophysiology, morphology and transcriptomics (using Smart-seq2 scRNA-seq)
  • Large-scale connectivity mapping across adult mouse brain-wide structures using rabies trans-synaptic tracing
  • Large-scale data generation and reconstruction of full neuronal morphologies from adult mouse brain-wide structures using fMOST and MouseLight
  • Generation of transgenic mouse lines targeting molecularly defined cell types from selected adult mouse cortical and subcortical structures

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