Abstract
Nadadhur et al. generated TSC disease models using patient iPSCs. While neuron mono-cultures showed an increase in network activity and dendritic branching, only when co-cultured with oligodendrocytes (OLs), hypertrophy and axonal abnormalities were observed. Neuron-OL interactions, modulated by mTOR regulators, support use of mixed cultures for TSC disease modeling and drug development.
Original language | English |
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Pages (from-to) | 42-56 |
Number of pages | 15 |
Journal | Stem cell reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 8 Jan 2019 |
Funding
A.G.N. and V.M.H. conceptualized and designed the experiments. V.M.H. provided iPSC/study material and financial support. A.G.N. performed, collected, and analyzed all the cell culture, immunofluorescence, and calcium imaging data. M.A. and A.J.H. performed the MEA analysis. L.G. supported the cell culture experiments and provided administrative support. P.C.S., E.v.H., and A.G.N. performed and analyzed the western blot experiments. S.D., V.M.H., and A.G.N. collected all transplantation data. A.G.N. and V.M.H. wrote the manuscript with inputs from all authors. We thank Prof. Eleonora Aronica for providing TSC patient material. We thank Gerbren Jacobs and Frank den Oudsten for help with iPSC and rat astrocyte cultures. We thank Joke Wortel and Nina Straat for performing transplantation and Carola Berkel for performing sequencing experiments. We thank Jurjen Broeke for valuable suggestions on calcium imaging experiments. We thank Nicole Breeuwsma and Jorik Methorst for help with immunohistochemistry and western blot. This study was supported and funded by Amsterdam Neuroscience and EU MSCA -ITN CognitionNet ( FP7-PEOPLE-2013-ITN 607508 ). M.A. and A.J.H. are supported by DEFINE, a Wellcome Trust Strategic Award (100202). V.M.H. is supported by ZonMw VIDI Research grant ( 91712343 ), E-Rare Joint Call project ( 9003037601 ) and a European Leukodystrophy Association (ELA) Research Grant ( 2014-012L1 ).
Funders | Funder number |
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Multiple Sclerosis Center of Atlanta | FP7-PEOPLE-2013-ITN 607508 |
Wellcome Trust | 100202 |
Seventh Framework Programme | 607508 |
ZonMw | 91712343, 9003037601 |
Association Européenne contre les Leucodystrophies | 2014-012L1 |
Keywords
- autism
- co-culture
- glia
- in vitro model
- iPSC
- myelin
- neuron
- neuronal activity
- oligodendrocyte
- tuberous sclerosis complex