Talk Title: Dynamic changes of brain cell types in development and aging

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 generated a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain, including >5,300 clusters that are hierarchically organized. Extending from this foundational reference atlas, we have investigated the dynamic changes of transcriptomic profiles of specific cell types in the developing and aging brain. In the aging mouse brain, through brain-wide single-cell transcriptomic profiling, we uncovered cell-type specific transcriptomic signatures of decreased neuronal structure and function and increased immune response and inflammation. We further identified a potential hotspot for aging involving specific hypothalamic cell types regulating energy homeostasis that exhibit both decreased neuronal function and increased immune response, suggesting a connection among metabolism, neuroinflammation, and aging. As a first deep characterization of brain development, we generated a transcriptomic and epigenomic cell type atlas of the developing mouse visual cortex, with dense temporal sampling from E11.5 to P28. We reconstructed a transcriptomic developmental trajectory map of all excitatory, inhibitory, and non-neuronal cell types in the visual cortex, which reveals continuous cell type diversification throughout the pre- and postnatal stages of cortical development. We also conducted an in-depth analysis of the transcriptomic and spatial organization of GABAergic neuron types (>1,000 clusters) in all regions of the mouse telencephalon and their developmental origins. We found that long-distance migration and dispersion is a common characteristic of nearly all these neuron types. In contrast to cortical and striatal GABAergic neurons which undergo extensive postnatal diversification, septal, preoptic and most pallidal GABAergic neuron types emerge in a burst during the embryonic stage with limited postnatal diversification, suggesting distinct cell-type development mechanisms in different brain regions.

Bio: Hongkui Zeng is Executive Vice President and Director of Brain Science at Allen Institute. She studies neuronal diversity and connectivity in the mammalian brain-wide circuits in the context of development, function and disease. Through her leadership of multidisciplinary teams, she has built research programs using transcriptomic, connectomic and multimodal approaches to characterize and classify the wide variety of cell types in the brain, laying the foundation for unraveling the cell type basis of brain function. Her work has led to many large-scale, open-access datasets and tools that have become widely adopted community resources and standards, including transgenic mouse lines, Allen Mouse Brain Connectivity Atlas, the Common Coordinate Framework (CCF), and the brain-wide transcriptomic cell type taxonomy and atlas. Zeng received her Ph.D. in molecular and cell biology from Brandeis University, where she studied the molecular mechanisms of the circadian clock in fruit flies. As a postdoctoral fellow at Massachusetts Institute of Technology, she studied the molecular and synaptic mechanisms underlying hippocampus-dependent plasticity and learning. She has received many honors, including the 2016 AWIS Award for Scientific Advancement, the 2018 Gill Transformative Investigator Award, the 2023 Pradel Research Award from the National Academy of Sciences, and the 2024 Asian American Engineer of the Year (AAEOY) Award. She is an elected member of the National Academy of Sciences and the National Academy of Medicine.

Followed by a reception with food and drink in 3^rd floor atrium