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Title 

Distinctive genomic signature of neural and intestinal organoids from familial Parkinson’s disease patient-derived induced pluripotent stem cells

Authors 

Mi Young SonHyuna SimYe Seul SonKwang Bo JungMi Ok LeeJ H OhS K ChungCho-Rok JungJanghwan Kim

Publisher 

Wiley

Issue Date 

2017

Citation 

Neuropathology and Applied Neurobiology

Keywords 

induced pluripotent stem cellintestinal organoidLRRK2microarrayneural progenitor cellneuroectodermal sphereParkinson's disease

Abstract 

Aims: The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature. Methods: We generated PD patient-specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three-dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses. Results: The expression profiles of LK2GS were distinct from those of wild-type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD-specific hNESs and hIOs by microarray and qRT-PCR analysis. Conclusion: We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids

ISSN 

0305-1846

Link 

http://dx.doi.org/10.1111/nan.12396

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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