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* **[COBREXA.jl: constraint-based reconstruction andexascale analysis]({{ "frozen/zkcr-bt30" | relative_url }})**
* **[Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-G2019S - associated gene expression]({{ "frozen/rc4f-nk07" | relative_url }})**
* **[Functional meta-omics provide critical insights into long and short read assemblies]({{ "frozen/sgzt-ad12" | relative_url }})**
* **[Protein Relative Abundance Quantification Algorithm for 3d fluorescent images from tissue]({{ "frozen/PRAQA" | relative_url }})**
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---
layout: default
order: -1
title: Midbrain organoids represent a physiologically relevant model that recapitulates PD-associated genetic signatures during early development
title: Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-G2019S - associated gene expression
permalink: /frozen/rc4f-nk07
---
{% rtitle Midbrain organoids represent a physiologically relevant model that recapitulates PD-associated genetic signatures during early development %}
Alise Zagare1,*, Kyriaki Barmpa1,*, Semra Smajic1, Lisa Smits1, Kamil Grzyb1, Anne Grünewald1, Alexander Skupin1, Sarah Louise Nickels1,° and Jens Christian Schwamborn1,2,°
1 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
2 OrganoTherapeurtics
*,° These authors share authorship
° Corresponding author: Sarah L. Nickels, Jens Christian Schwamborn
permalink: [doi:10.17881/rc4f-nk07](https://doi.org/10.17881/rc4f-nk07)
{% rtitle Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-G2019S - associated gene expression %}
Alise Zagare, Kyriaki Barmpa, Semra Smajic, Lisa Smits, Kamil Grzyb, Anne Grünewald, Alexander Skupin, Sarah Louise Nickels and Jens Christian Schwamborn
{% endrtitle %}
{% rblock Abstract %}
Human brain organoid models that recapitulate the physiology and complexity of the human brain have a great potential for in vitro disease modeling, in particular for neurodegenerative diseases, such as Parkinson’s disease. In the present study, we compare single-cell RNA sequencing data of human midbrain organoids to the developing human embryonic midbrain. We demonstrate that the in vitro model is comparable to its in vivo equivalents in terms of developmental path and cellular composition. Moreover, we investigate the potential of midbrain organoids for modeling early developmental changes in Parkinson’s disease. Therefore, we compare the single cell-RNA sequencing data of healthy individual-derived midbrain organoids to their isogenic LRRK2-G2019S inserted/mutated counterparts. We show that the LRRK2-G2019S mutation alters neurodevelopment, resulting in an untimely and incomplete differentiation with reduced cellular variability. Finally, we present four candidate genes APP, DNAJC6, GATA3 and PTN that might contribute to the LRRK2-G2019S associated transcriptome changes during early neurodevelopment.
{% endrblock %}
Modeling neurodegenerative diseases, such as Parkinson’s, can be difficult, since human brain physiology and disease complexity are not reached in the majority of commonly used laboratory models. Here we question the potency of human-derived midbrain organoids in Parkinson’s disease research by following two different approaches; by investigating their similarity to the developing human midbrain and their ability to recapitulate the disease phenotype. We integrate the transcriptomes of midbrain organoids and human embryonic midbrain to show that organoids represent an accurate system for disease modeling. They reflect not only the human midbrain development but also depict the Parkinson’s disease associated genetic signature. Our work heightens the beneficial contributions of organoids as an appropriate model for studying diseases in vitro.
{% rgridblock a-unique-id %}
{% rblock Raw data | fas fa-database %}
The complete Dataset is available [here](https://webdav-r3lab.uni.lu/public/data/rc4f-nk07/). It is subdivided into originals (raw data) and partials (analysis) specific to each figure and supplementary figure present in the manuscript.
{% endrblock %}
{% rblock Raw Data %}
The complete Dataset is available [here](). It is subdivided into originals (raw data) and partials (analysis) specific to each figure and supplementary present in the manuscript.
{% rblock RNA-seq data | fas fa-database %}
The different RNA-seq datasets used in the study are available here: [Embryo Cortex - GSE104276](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE104276); [Embryo Midbrain - GSE76381](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE76381) and [Cortex Organoid - GSE130238](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE130238).
{% endrblock %}
{% rblock Scripts %}
The source code used to make the analysis/figures of the publication is available [on Github](https://github.com/LCSB-DVB/Zagare_Barmpa_2021).
{% endrblock %}
{% endrgridblock %}
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