Dr. Hongkui Zeng

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This week, we profile a recent publication in Cell from Hongkui Zeng (pictured) at Allen Institute for Brain Science.

Can you provide a brief overview of your lab’s current research focus?
Our team at the Allen Institute for Brain Science studies cell type diversity in the mouse and human brains. To understand the function of the brain and how its dysfunction leads to brain diseases, an essential first step is to obtain a “parts list” of the brain, i.e. to uncover the vast range of neuronal and nonneuronal cell types and their properties and then try to understand how they work together. We have built multiple technology platforms to characterize the transcriptomic (gene expression), physiological, morphological, and connectional properties of brain cell types in a systematic manner. Computational analyses of these large-scale datasets lead to a multi-modal integrated taxonomy and atlas of cell types in the mouse cortex and other brain regions. These studies reveal extraordinary cellular diversity and underlying rules of brain organization and lay the foundation for unraveling mechanisms of brain function.

What is the significance of the findings in this publication?
In this study, we generated single-cell transcriptomes from >1.3 million cells in the mouse neocortex and hippocampal formation, two major brain structures critical for the cognitive function of the brain, and classified them into 388 cell types. We identified many new cell types in specific regions of these two structures as well as large-scale gradients of cell types shared across multiple regions. We found that despite the highly distinct nature between the cell types in the neocortex and hippocampal formation, the two sets of cell types are also homologous to each other and there is an underlying parallel cell-type and circuit organization between the two structures. This finding suggests that contrary to the traditional view of hippocampal formation being an older and simpler brain structure compared to the neocortex, these two major structures in the mammalian brain have co-evolved from the ancestral reptile brain to acquire new cell types and functions. Our study establishes a first comprehensive cell type catalog of the mammalian isocortex and hippocampal formation and begins to shed light on its underlying relationship with the development, evolution, connectivity, and function of these two brain structures.

What are the next steps for this research?
Our goal is to create a comprehensive cell type catalog and atlas for the entire mouse brain, the first in mammals, and ultimately a similar cell type atlas for the human brain. We have already generated a large set of single-cell transcriptomic data in many other parts of the mouse brain and are analyzing the data to investigate the composition of cell types and the relationship among them across different brain regions. This kind of study provides very interesting hints of the evolutionary and developmental origins of cell types. Furthermore, we will continue to study the anatomical and physiological properties of these cell types and how they might change in various behavioral or diseased conditions, to understand how these cell types contribute to brain function.

This work was funded by:
This work was funded by multiple grant awards from institutes under the National Institutes of Health, including National Eye Institute (R01EY023173), National Institute of Mental Health (U01MH105982, U19MH114830), and Eunice Kennedy Shriver National Institute of Child Health & Human Development (U01MH105982), and by the Allen Institute for Brain Science.

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