Generation of human midbrain organoids from induced pluripotent stem cells
Open Access
- 3 April 2019
- journal article
- Published by F1000 Research Ltd in MNI Open Research
Abstract
The development of brain organoids represents a major technological advance in the stem cell field, a novel bridge between traditional 2D cultures and in vivo animal models. In particular, the development of midbrain organoids containing functional dopaminergic neurons producing neuromelanin granules, a by-product of dopamine synthesis, represents a potential new model for Parkinson’s disease. To generate human midbrain organoids, we introduce specific inductive cues, at defined timepoints, during the 3D culture process to drive the stem cells towards a midbrain fate. In this method paper, we describe a standardized protocol to generate human midbrain organoids (hMOs) from induced pluripotent stem cells (iPSCs). This protocol was developed to demonstrate how human iPSCs can be successfully differentiated into numerous, high quality midbrain organoids in one batch. We also describe adaptations for cryosectioning of fixed organoids for subsequent histological analysis.Keywords
Funding Information
- Parkinson Canada
- Fonds de Recherche du Québec - Santé
- Canadian Institutes of Health Research
- Michael J. Fox Foundation
- Consortium québécois sur la découverte du médicament
- Van Berkom-Saucier Foundation
- Fonds de Recherche du Québéc-Santé Quebec Parkinson Network
- Parkinson’s Canada New Investigator Award
This publication has 62 references indexed in Scilit:
- Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's diseaseNeurobiology of Disease, 2018
- Crosstalk between Lysosomes and Mitochondria in Parkinson's DiseaseFrontiers in Cell and Developmental Biology, 2017
- Impaired nigrostriatal function precedes behavioral deficits in a genetic mitochondrial model of Parkinson's diseaseThe FASEB Journal, 2011
- A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old MicePLOS ONE, 2010
- Mitochondrial Dysfunction in Parkinson's DiseaseJournal of Alzheimer's Disease, 2010
- Parkinson's Disease Patient-Derived Induced Pluripotent Stem Cells Free of Viral Reprogramming FactorsCell, 2009
- The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in DrosophilaProceedings of the National Academy of Sciences of the United States of America, 2008
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Suppression of basal autophagy in neural cells causes neurodegenerative disease in miceNature, 2006
- Parkinson's Disease in a Chemist Working with 1-Methyl-4-Phenyl-L,2,5,6-TetrahydropyridineThe New England Journal of Medicine, 1983