A Rapid Pipeline to Model Rare Neurodevelopmental Disorders with Simultaneous CRISPR/Cas9 Gene Editing.
The development of targeted therapeutics for rare neurodevelopmental disorders (NDDs) faces significant challenges due to the scarcity of subjects and the difficulty of obtaining human neural cells. Here, we illustrate a rapid, simple protocol by which patient derived cells can be reprogrammed to induced pluripotent stem cells (iPSCs) using an episomal vector and differentiated into neurons. Using this platform enables patient somatic cells to be converted to physiologically active neurons in less than two months with minimal labor. This platform includes a method to combine somatic cell reprogramming with CRISPR/Cas9 gene editing at single cell resolution, which enables the concurrent development of clonal knockout or knock-in models that can be used as isogenic control lines. This platform reduces the logistical barrier for using iPSC technology, allows for the development of appropriate control lines for use in rare neurodevelopmental disease research, and establishes a fundamental component to targeted therapeutics and precision medicine. Stem Cells Translational Medicine 2017;6:886-896.
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Scott
S
Bell
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Huashan
H
Peng
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Liam
L
Crapper
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Ilaria
I
Kolobova
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Gilles
G
Maussion
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Cristina
C
Vasuta
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.
Volodymyr
V
Yerko
Departments of Psychiatry, McGill University, Montreal, Quebec, H4H 1R3, Canada.
Tak Pan
TP
Wong
McGill Group for Suicide Studies, Douglas Hospital Research Institute, Montreal, Quebec, H4H 1R3, Canada.|Departments of Psychiatry, McGill University, Montreal, Quebec, H4H 1R3, Canada.|Human Genetics, McGill University, Montreal, Quebec, H4H 1R3, Canada.
Carl
C
Ernst
D001483:Base Sequence; D000076987:CRISPR-Associated Protein 9 / Q000378:metabolism*; D064113:CRISPR-Cas Systems / Q000235:genetics*; D002454:Cell Differentiation; D005347:Fibroblasts / Q000473:pathology; D000072669:Gene Editing; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism; D008636:Mesencephalon / Q000473:pathology; D008954:Models, Biological; D065886:Neurodevelopmental Disorders / Q000473:pathology*; D009474:Neurons / Q000473:pathology; D016548:Prosencephalon / Q000473:pathology
D000076987:CRISPR-Associated Protein 9
Clinical utility; Dopamine; Gene editing; Glutamate; Induced pluripotent stem cells; Neurodevelopment