Neuron-Glia Interactions Increase Neuronal Phenotypes in Tuberous Sclerosis Complex Patient iPSC-Derived Models

Aishwarya G. Nadadhur, Mouhamed Alsaqati, Lisa Gasparotto, Paulien Cornelissen-Steijger, Eline van Hugte, Stephanie Dooves, Adrian J. Harwood, Vivi M. Heine*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)42-56
Number of pages15
JournalStem cell reports
Volume12
Issue number1
DOIs
Publication statusPublished - 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 ).

FundersFunder number
Multiple Sclerosis Center of AtlantaFP7-PEOPLE-2013-ITN 607508
Wellcome Trust100202
Seventh Framework Programme607508
ZonMw91712343, 9003037601
Association Européenne contre les Leucodystrophies2014-012L1

    Keywords

    • autism
    • co-culture
    • glia
    • in vitro model
    • iPSC
    • myelin
    • neuron
    • neuronal activity
    • oligodendrocyte
    • tuberous sclerosis complex

    Fingerprint

    Dive into the research topics of 'Neuron-Glia Interactions Increase Neuronal Phenotypes in Tuberous Sclerosis Complex Patient iPSC-Derived Models'. Together they form a unique fingerprint.

    Cite this