Hongkui Zeng, PhD

Executive Vice President, Director of Allen Institute for Brain Science

Allen Institute

Host(s): Steven Kushner (Faculty), Joseph Gogos (Faculty)

Dynamic changes of brain cell types in development and aging

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.

Relevant Publications: 

A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

Brain-wide-cell-type-specific transcriptomic signatures of healthy ageing in mice 

Tuesdays@10 is a signature Zuckerman Institute initiative that aims to expose researchers at all levels to high-quality science and stimulate scientific discourse. The speakers featured in this series represent various fields and techniques in neuroscience, and include invited guests of the Columbia Neuroscience Seminars, the Zuckerman Institute's Local Circuits Affiliates Program, and other special seminar series through a combined, collaborative effort of one or more of the following: Columbia's Zuckerman Institute, the Center for Precision Psychiatry, the Center for Theoretical Neuroscience, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science. 

More information and a full schedule can be found here.