NB-CNS Seminar - Hongkui Zeng
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 longdistance
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.