Research Focus:

The brain circuit is an intricately interconnected network of a vast number of neurons with diverse molecular, anatomical and physiological properties. To understand the principles of information processing in the brain circuit, it is essential to have comprehensive knowledge about the common and unique properties of its components - the neuronal as well as non-neuronal cell types, to monitor their activities while the brain is processing information, and to have the ability to manipulate these cells to investigate their functions in the brain circuit. Combining genetic tools with large-scale imaging and single-cell analysis technologies presents us with the opportunity to gain systematic understanding of the properties, interconnections and functions of these cell types.

Zeng’s team at the Allen Institute has built multiple platforms, including single-cell transcriptomics, spatial transcriptomics, single and multi-patching electrophysiology, 3D reconstruction of neuronal morphology, high throughput brain-wide connectivity mapping, large-scale electron microscopy connectomics, and cell type-targeting transgenic and viral tools, to characterize the transcriptomic, physiological, morphological, and connectional properties of different types of mammalian brain cells in a standardized way. Zeng has been the principal investigator on several large National Institutes of Health-funded projects, including a BRAIN Initiative Cell Census Network (BICCN) project in which her team created a comprehensive whole-brain atlas of cell types in the mouse, and two BRAIN Initiative Cell Atlas Network (BICAN) projects with the goals of creating similarly comprehensive and high-resolution cell type atlases for human and non-human primate (NHP) brains and for the developmental mouse brain.

The Allen Institute team Zeng leads has utilized these platforms to define and classify the diverse cell types that constitute the mammalian brain and describe their wiring diagrams at different levels, uncovering principles of cell type and circuit organization including the hierarchical organization reflecting the varied similarities and differences among cell types, the coexistence of discrete and continuous transcriptional variations across cell types, the correspondence as well as nuanced heterogeneities at granular levels between transcriptomic profiles and other modalities of cellular properties, and the conservation and divergence of cell types across species. The Allen team has been building the online Brain Knowledge Platform to provide all the data, knowledge and tools as comprehensive foundational resources to the broader neuroscience community. Zeng’s research has also moved beyond cell atlasing, further into studies of cell type and cell state changes during developmental, aging, behavioral, pharmacological, and diseased processes, revealing new relationships between spatiotemporal transcriptomic dynamics and cell type-specific functions. Altogether, building such an integrated and dynamic cell type knowledge base lays the foundation for decoding the computational mechanisms of brain circuit function.