Understanding neural development and diseases using CRISPR screens in human pluripotent stem cell-derived cultures

被引:5
作者
Ahmed, Mai [1 ]
Muffat, Julien [2 ,3 ]
Li, Yun [1 ,3 ]
机构
[1] Hosp Sick Children, Program Dev & Stem Cell Biol, Toronto, ON, Canada
[2] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON, Canada
[3] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2023年 / 11卷
关键词
CRISPR; human pluripotent stem cell (hPSC); neurodevelopment; neurological disease; genetic screens; organoids; MICROGLIA-LIKE CELLS; GENETIC SCREENS; DIRECTED DIFFERENTIATION; CEREBRAL ORGANOIDS; ZIKA VIRUS; CORTICAL INTERNEURONS; HEXANUCLEOTIDE REPEAT; POOLED SCREENS; IN-VITRO; GENERATION;
D O I
10.3389/fcell.2023.1158373
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The brain is arguably the most complex part of the human body in form and function. Much remains unclear about the molecular mechanisms that regulate its normal and pathological physiology. This lack of knowledge largely stems from the inaccessible nature of the human brain, and the limitation of animal models. As a result, brain disorders are difficult to understand and even more difficult to treat. Recent advances in generating human pluripotent stem cells (hPSCs)-derived 2-dimensional (2D) and 3-dimensional (3D) neural cultures have provided an accessible system to model the human brain. Breakthroughs in gene editing technologies such as CRISPR/Cas9 further elevate the hPSCs into a genetically tractable experimental system. Powerful genetic screens, previously reserved for model organisms and transformed cell lines, can now be performed in human neural cells. Combined with the rapidly expanding single-cell genomics toolkit, these technological advances culminate to create an unprecedented opportunity to study the human brain using functional genomics. This review will summarize the current progress of applying CRISPR-based genetic screens in hPSCs-derived 2D neural cultures and 3D brain organoids. We will also evaluate the key technologies involved and discuss their related experimental considerations and future applications.
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页数:14
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