Modeling Parkinson's Disease in Midbrain-like Organoids

Overview

Journal NPJ Parkinsons Dis

Date 2019 Apr 10

PMID 30963107

Citations 144

Authors

Lisa M Smits

Lydia Reinhardt

Peter Reinhardt

Michael Glatza

Anna S Monzel

Nancy Stanslowsky

Marcelo D Rosato-Siri

Alessandra Zanon

Paul M Antony

Jessica Bellmann

Sarah M Nicklas

Kathrin Hemmer

Xiaobing Qing

Emanuel Berger

Norman Kalmbach

Marc Ehrlich

Silvia Bolognin

Andrew A Hicks

Florian Wegner

Jared L Sterneckert

Jens C Schwamborn

Affiliations

Soon will be listed here.

Abstract

Modeling Parkinson's disease (PD) using advanced experimental in vitro models is a powerful tool to study disease mechanisms and to elucidate unexplored aspects of this neurodegenerative disorder. Here, we demonstrate that three-dimensional (3D) differentiation of expandable midbrain floor plate neural progenitor cells (mfNPCs) leads to organoids that resemble key features of the human midbrain. These organoids are composed of midbrain dopaminergic neurons (mDANs), which produce and secrete dopamine. Midbrain-specific organoids derived from PD patients carrying the G2019S mutation recapitulate disease-relevant phenotypes. Automated high-content image analysis shows a decrease in the number and complexity of mDANs in G2019S compared to control organoids. The floor plate marker FOXA2, required for mDAN generation, increases in PD patient-derived midbrain organoids, suggesting a neurodevelopmental defect in mDANs expressing G2019S. Thus, we provide a robust method to reproducibly generate 3D human midbrain organoids containing mDANs to investigate PD-relevant patho-mechanisms.

Citing Articles

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