Towards elucidating disease-relevant states of neurons and glia by CRISPR-based functional genomics

Our understanding of neurological diseases has been tremendously enhanced over the past decade by the application of new technologies. Genome-wide association studies have highlighted glial cells as important players in diseases. Single-cell profiling technologies are providing descriptions of disease states of neurons and glia at unprecedented molecular resolution. However, significant gaps remain in our understanding of the mechanisms driving disease-associated cell states, and how these states contribute to disease. These gaps in our understanding can be bridged by CRISPR-based functional genomics, a powerful approach to systematically interrogate gene function. In this review, we will briefly review the current literature on neurological disease-associated cell states and introduce CRISPR-based functional genomics. We discuss how advances in CRISPR-based screens, especially when implemented in the relevant brain cell types or cellular environments, have paved the way towards uncovering mechanisms underlying neurological disease-associated cell states. Finally, we will delineate current challenges and future directions for CRISPR-based functional genomics to further our understanding of neurological diseases and potential therapeutic strategies.

Automated summary

Our understanding of neurological diseases has been greatly improved by new technologies. Glial cells have been identified as important in diseases, and single-cell profiling technologies describe disease states of neurons and glia at a molecular level. However, there are still gaps in understanding the mechanisms and contributions of disease-associated cell states, which can be filled by CRISPR-based functional genomics.