Presenter: Hongkui Zeng, Executive Vice President, Director of the Allen Institute for Brain Science

Abstract: To understand the function of the brain and how its dysfunction leads to brain diseases, it is essential to uncover the cell type composition of the brain, how the cell types are connected with each other and what their roles are in circuit function. At the Allen Institute, we have built multiple technology platforms, including single-cell transcriptomics, spatial transcriptomics, single and multi-patching electrophysiology, 3D reconstruction of neuronal morphology, and brain-wide connectivity mapping, to characterize the molecular, anatomical, physiological, and connectional properties of brain cell types in a systematic manner, towards the creation of multi-modal cell atlases for the mouse and human brains­.

We have now generated a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain, based on the combination of two single-cell-level, whole-brain-scale datasets by scRNA-seq and MERFISH. The atlas is hierarchically organized into five nested levels of classification: 7 divisions, 32 classes, ~300 subclasses, ~1,000 supertypes and ~5,200 clusters. We systematically analyzed the neuronal, non-neuronal, and immature neuronal cell types across the brain and identified a high degree of correspondence between transcriptomic identity and spatial specificity for each cell type. The study uncovered tremendous heterogeneity in neurotransmitter and neuropeptide expression and co-expression patterns in different cell types, suggesting they mediate myriad modes of intercellular communications. We also found that transcription factors are major determinants of cell type classification in the adult mouse brain and identified a combinatorial transcription factor code that defines cell types across all parts of the brain. This study reveals extraordinary cellular diversity and underlying rules of brain organization. It establishes a benchmark reference atlas and a foundational resource for deep and integrative investigations of cell type and circuit function, development, and evolution of the mammalian brain.

Room: Picasso + Machado

A key current question in neuroscience is “What cell types are present in the healthy human brain?” Understanding the basic components of the brain and their development will help us understand how the brain functions typically and serve as a starting point for understanding what goes wrong in disease. This symposium features speakers from four groups leading work on aspects of brain cell type characterization. Their work is part of a broader NIH-led movement towards developing comprehensive, granular cell atlases of the healthy neurotypical brain, directly linking structural and functional properties to underlying cellular and molecular architecture, and doing so across species and developmental time. The Allen Institute has created multiple adult mammalian brain cell atlases and will release a whole mouse brain atlas in early 2023, which Jeremy Miller has contributed to. Sten Linnarsson’s lab, represented by Kimberly Siletti, has developed and applied novel technologies for the identification of cell types in mouse and human brain. Xiaowei Zhuang’s lab has developed a prominent spatial transcriptomics methodology (MERFISH) and used this to localize cell types across mouse and human tissues. Tom Nowakowski continues to co-lead efforts at understanding how brain cell types emerge and transform during development. These groups present complementary building blocks to lay the groundwork for a comprehensive census of cell types in the healthy developing and adult human brain. More session information

Chair:

• Hongkui Zeng, Allen Institute for Brain Science 

Presenters:

• Jeremy Miller, Allen Institute for Brain Science 
• Kimberly Siletti, Karolinska Institute 

• Xiaowei Zhuang, Harvard University 
• Tomasz Nowakowski, UCSF 

Room:

• Picasso + Machado 

The Allen Institute for Brain Science has released several cell type taxonomies, along with tools aimed at exploring these brain cell types and comparing them with data collected from other scientists. In addition to the focus on high-throughput single cell transcriptomics, these resources also touch on additional features of brain cell types, including their electrophysiology, morphology, anatomic localization, and underlying genetics. At this tutorial, attendees will learn how to access Allen Institute cell type taxonomies and will walk through technical tools that enable scientists to navigate these taxonomies. Topics include: 

1. What is a cell type taxonomy? 
2. How do I compare my single cell RNA-sequencing data with a reference taxonomy? 
3. Besides their genes expressed, what are the features of cell types in primary motor cortex? 
4. What kinds of cells are found in human cortex and how do they change in Alzheimer’s disease? 

We will start with a focus on primary motor cortex (MOp), where attendees will first briefly learn about the Cell Types Database: RNA-Seq Data and the included tools for data download and exploration. Most of the workshop will focus on the Cell Type Knowledge Explorer (CTKE), which is an interactive application that aggregates many types of data at the level of individual cell types in mouse, human and marmoset. Attendees will then get a brief introduction to an atlas extending cell typing efforts to the entire mouse brain, along with resources for deeper exploration outside of the tutorial. Finally, we will explore tools developed as part of the Seattle Alzheimer’s Disease Brain Cell Atlas (SEA-AD) exploring cell types in the adult human cortex and how these cell types change in normal aging and disease. 

Attendees should bring a laptop to this tutorial to interactively explore the website during instruction. No coding experience is required. 

Presenters:

• Jeremy Miller, Allen Institute for Brain Science 
• Kaitlyn Casimo, Allen Institute

Room:

• Sala U1
  

Poster session E: AS18 History, Teaching, and Neuro-ethics

Board number: E46

September 10, 14:45-19:30

Poster session E: AS15 Transcriptomics, Genomics, and Epigenomics

Board number: E21

September 10, 08:30-13:45