Hongkui Zeng: Dynamic changes of brain cell types in aging, development and behaviors

Speaker: Hongkui Zeng, Allen Institute for Brain Science, Seattle, WA, USA

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

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. To reveal the evolutionary conservation and divergence of cell types in the mammalian brain, we are creating similarly high-resolution cell type atlases for human and non-human primate brains and computationally integrating them into cross-species aligned cell type taxonomies. 

Extending from these foundational reference atlases, we have investigated the dynamic changes of transcriptomic profiles of specific cell types in the aging and developing brain, as well as under various behavioral conditions. In the 18-month-old aging mouse brain in comparison with 2-month-old young adult 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. We extended the aging study to 24-month-old mice and began to reveal age-dependent transcriptomic dynamics in brain-wide neuronal and non-neuronal cell types. These findings will facilitate deeper investigation to reveal new insights into brain cell type diversity and their dynamic changes in different cell states.