A guide to generating and using hiPSC derived NPCs for the study of neurological diseases

Journal of Visualized Experiments : JoVE
Aaron TopolKristen J Brennand

Abstract

Post-mortem studies of neurological diseases are not ideal for identifying the underlying causes of disease initiation, as many diseases include a long period of disease progression prior to the onset of symptoms. Because fibroblasts from patients and healthy controls can be efficiently reprogrammed into human induced pluripotent stem cells (hiPSCs), and subsequently differentiated into neural progenitor cells (NPCs) and neurons for the study of these diseases, it is now possible to recapitulate the developmental events that occurred prior to symptom onset in patients. We present a method by which to efficiently differentiate hiPSCs into NPCs, which in addition to being capable of further differentiation into functional neurons, can also be robustly passaged, freeze-thawed or transitioned to grow as neurospheres, enabling rapid genetic screening to identify the molecular factors that impact cellular phenotypes including replication, migration, oxidative stress and/or apoptosis. Patient derived hiPSC NPCs are a unique platform, ideally suited for the empirical testing of the cellular or molecular consequences of manipulating gene expression.

Citations

Dec 3, 2015·Methods : a Companion to Methods in Enzymology·Seok-Man HoKristen J Brennand
Oct 26, 2018·Nature Communications·Benjamin ReadheadKristen J Brennand
Aug 10, 2019·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Guang Yang, Alex Shcheglovitov
May 7, 2020·Anesthesia and Analgesia·Detlef ObalVivianne L Tawfik
Dec 13, 2017·Molecular Neuropsychiatry·Ifeanyi V ObiorahKristen J Brennand
Dec 1, 2019·Nature Genetics·Erin FlahertyKristen J Brennand
Mar 26, 2021·Molecular Biology Reports·Laura da Silva SiqueiraDaniel Rodrigo Marinowic
May 26, 2021·Nature Neuroscience·Ruilin TianMartin Kampmann

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