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

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Mai Ahmed¹  Yun Li²  Julien Muffat³ 

[1] Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada;Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada;Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada;Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada;Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada;

关键词: CRISPR;    human pluripotent stem cell (hPSC);    neurodevelopment;    neurological disease;    genetic screens;    organoids;   

DOI  :  10.3389/fcell.2023.1158373

 received in 2023-02-03, accepted in 2023-03-30,  发布年份 2023

来源: Frontiers

【 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.

【 授权许可】

Unknown   
Copyright © 2023 Ahmed, Muffat and Li.