@article{d64e7f91294d468ebe85b0d7a2c99746,
title = "A Human Neuron/Astrocyte Co-culture to Model Seeded and Spontaneous Intraneuronal Tau Aggregation",
abstract = "Communication and contact between neurons and astrocytes is important for proper brain physiology. How neuron/astrocyte crosstalk is affected by intraneuronal tau aggregation in neurodegenerative tauopathies is largely elusive. Human induced pluripotent stem cell (iPSC)-derived neurons provide the opportunity to model tau pathology in a translationally relevant in vitro context. However, current iPSC models inefficiently develop tau aggregates, and co-culture models of tau pathology have thus far utilized rodent astrocytes. In this article, we describe the co-culture of human iPSC-derived neurons with primary human astrocytes in a 96-well format compatible with high-content microscopy. By lentiviral overexpression of different mutated tau variants, this protocol can be flexibly adapted for the efficient induction of seeded or spontaneous tau aggregation. We used this novel co-culture model to identify cell type–specific disease mechanisms and to provide proof of concept for intervention by antisense therapy. These results show that this human co-culture model provides a highly translational tool for target discovery and drug development for human tauopathies.",
keywords = "astrocytes, co-culture, induced pluripotent stem cell, neurons, tau pathology",
author = "Batenburg, {Kevin Llewelyn} and Rohde, {Susan Karijn} and Paulien Cornelissen-Steijger and Nicole Breeuwsma and Heine, {Vivi Majella} and Wiep Scheper",
note = "Funding Information: This study was supported by ZonMW and Stichting Proefdiervrij (MKMD no. 114022506 to WS) and co‐funded by the PPP Allowance made available by Health∼Holland, Top Sector Life Sciences & Health, to stimulate public‐private partnerships (no. LSHM17014 to VMH and LSHM18024 to WS). Funding Information: This study was supported by ZonMW and Stichting Proefdiervrij (MKMD no. 114022506 to WS) and co-funded by the PPP Allowance made available by Health∼Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships (no. LSHM17014 to VMH and LSHM18024 to WS). The authors thank Nael Nadif Kasri for providing the Ngn2 human iPSC line; Lisa Gasparotto for advice and expert technical assistance on human iPSC cultures; and Robbert Zalm, Ingrid Saarloos, and Joost Hoetjes for preparation of constructs and viral particles. The authors also thank Peter Davies (Albert Einstein College of Medicine, New York, New York) for providing the MC1 antibody. The authors thank Vera Wiersma for expert advice on seeded FTDtau1 aggregation and members of the Molecular Neurodegeneration group (Functional Genomics, Vrije Universiteit, Amsterdam, Netherlands) and the Stem Cell Biology group (Complex Trait Genetics, Vrije Universiteit, Amsterdam, Netherlands) for stimulating discussions. Publisher Copyright: {\textcopyright} 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.",
year = "2023",
month = oct,
day = "1",
doi = "https://doi.org/10.1002/cpz1.900",
language = "English",
volume = "3",
pages = "e900",
journal = "Current protocols",
issn = "2691-1299",
publisher = "John Wiley & Sons Inc.",
number = "10",
}