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

期刊

GENOME MEDICINE
卷 14, 期 1, 页码 -

出版社

BMC
DOI: 10.1186/s13073-022-01134-7

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资金

  1. NIH/NIA [F30 AG066418, R01 AG062359, U01 AG072464]
  2. NIH/NINDS [U54 NS123746]
  3. Alzheimer's Association
  4. Rainwater Charitable Foundation/Tau Consortium
  5. Chan Zuckerberg Initiative Neurodegeneration Challenge Network's Ben Barres Early Career Acceleration Award

向作者/读者索取更多资源

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.
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.

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