Dynamic changes of brain cell types in development and aging

Dr. Hongkui Zeng is the Executive Vice President & Director of the Allen Institute for Brain Science.

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 generated a comprehensive and high-resolution transcriptomic and spatial cell type atlas for the whole adult mouse brain, hierarchically organized into four nested levels of classification: 34 classes, 338 subclasses, 1,201 supertypes and 5,322 clusters. Extending from this foundational reference atlas, we have investigated the dynamic changes of transcriptomic profiles in the developing and aging brain. We generated a transcriptomic and epigenomic cell type atlas of the developing mouse visual cortex, with dense temporal sampling from E11.5 to P56. 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. 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, which is the hypothalamic region around the third ventricle, involving tanycytes, ependymal cells, and specific neuronal types with functional roles in energy homeostasis that exhibit both a decrease in neuronal function and an increase in immune response, suggesting a connection among metabolism, neuroinflammation, and aging.

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Hosted by Dr. Laura Colgin

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