Bosiljka Tasić
Allen Institute for Brain Science, Seattle, USA
bosiljkat [at] alleninstitute.org
Abstract
The human brain is an incredibly complex organ, composed of over 150 billion cells that work together to create consciousness and ultimately, define who we are. Abnormal function or death of specialized cell types cause various brain diseases.
Understanding how brain structure produces its function is the key goal of neuroscience. To define brain structure, we need to identify the types of building blocks (cell types) and their relationships. Then we need to eliminate or inactivate them and observe the consequences (e.g., inability to perform an action, like movement). Ethical barriers prevent us from using this approach in humans.
Mus musculus, the house mouse, is a dominant model for studying mammalian brains. Despite its small size, the mouse performs diverse behaviors common across mammals, including sophisticated movements and learning.
The Allen Institute for Brain Science stands at the forefront of defining cell type identity and function in the mammalian brain. Starting with single-cell transcriptomics followed by measurements of other cellular properties including morphology and electrophysiology, we created an extensive repository of brain single-cell data. We employed various bioinformatics approaches to analyze these multidimensional and multimodal data to define cell identity and cell types. We showed that the mouse brain contains at least 5000 cell types of which many exist in humans.
To assess cell type function, we used our single-cell measurements of chromatin accessibility to define putative enhancer elements in the mouse and human genome. When included in innocuous viruses, these enhancers can instruct expression of various molecular tools in specific cell types to probe their function in the brain.
Starting with mice and with an eye towards humans, the Allen Institute is building genetic tools for all cell types in mammalian brains. Coupled with advanced computational tools, our ability to understand the roles of all brain cell types in health and disease and modify their function toward cures is within reach.
Keywords: single-cell transcriptomics, cell types, mouse brain, genomics, enhancers
Acknowledgement: This work is the result of a large team of scientists at the Allen Institute for Brain Science and its collaborators. The work was supported by the United States National Institutes of Health Grants: U19MH114830 to Hongkui Zeng, RF1MH121274 to B.T. and Tanya Daigle, RF1MH114126 and UG3MH120095 to Boaz Levi, Jonathan Ting and Ed Lein, and UF1MH128339 to B.T., Jonathan Ting, Boaz Levi, Trygve Bakken and Tanya Daigle.