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Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function

Ohtonen, Sohvi ; Giudice, Luca ; Jäntti, Henna ; Fazaludeen, Mohammad Feroze ; Shakirzyanova, Anastasia ; Gómez-Budia, Mireia ; Välimäki, Nelli Noora ; Niskanen, Jonna ; Korvenlaita, Nea and Fagerlund, Ilkka , et al. (2023) In Scientific Reports 13(1).
Abstract

LRRK2-G2019S is one of the most common Parkinson’s disease (PD)-associated mutations and has been shown to alter microglial functionality. However, the impact of LRRK2-G2019S on transcriptional profile of human induced pluripotent stem cell-derived microglia-like cells (iMGLs) and how it corresponds to microglia in idiopathic PD brain is not known. Here we demonstrate that LRRK2-G2019S carrying iMGL recapitulate aspects of the transcriptional signature of human idiopathic PD midbrain microglia. LRRK2-G2019S induced subtle and donor-dependent alterations in iMGL mitochondrial respiration, phagocytosis and cytokine secretion. Investigation of microglial transcriptional state in the midbrains of PD patients revealed a subset of microglia... (More)

LRRK2-G2019S is one of the most common Parkinson’s disease (PD)-associated mutations and has been shown to alter microglial functionality. However, the impact of LRRK2-G2019S on transcriptional profile of human induced pluripotent stem cell-derived microglia-like cells (iMGLs) and how it corresponds to microglia in idiopathic PD brain is not known. Here we demonstrate that LRRK2-G2019S carrying iMGL recapitulate aspects of the transcriptional signature of human idiopathic PD midbrain microglia. LRRK2-G2019S induced subtle and donor-dependent alterations in iMGL mitochondrial respiration, phagocytosis and cytokine secretion. Investigation of microglial transcriptional state in the midbrains of PD patients revealed a subset of microglia with a transcriptional overlap between the in vitro PD-iMGL and human midbrain PD microglia. We conclude that LRRK2-G2019S iMGL serve as a model to study PD-related effects in human microglia.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
issue
1
article number
22118
publisher
Nature Publishing Group
external identifiers
  • pmid:38092815
  • scopus:85179714037
ISSN
2045-2322
DOI
10.1038/s41598-023-49294-9
language
English
LU publication?
yes
id
0ba4fca4-3157-4733-924b-51347da2a664
date added to LUP
2024-01-04 11:45:23
date last changed
2024-04-19 08:01:24
@article{0ba4fca4-3157-4733-924b-51347da2a664,
  abstract     = {{<p>LRRK2-G2019S is one of the most common Parkinson’s disease (PD)-associated mutations and has been shown to alter microglial functionality. However, the impact of LRRK2-G2019S on transcriptional profile of human induced pluripotent stem cell-derived microglia-like cells (iMGLs) and how it corresponds to microglia in idiopathic PD brain is not known. Here we demonstrate that LRRK2-G2019S carrying iMGL recapitulate aspects of the transcriptional signature of human idiopathic PD midbrain microglia. LRRK2-G2019S induced subtle and donor-dependent alterations in iMGL mitochondrial respiration, phagocytosis and cytokine secretion. Investigation of microglial transcriptional state in the midbrains of PD patients revealed a subset of microglia with a transcriptional overlap between the in vitro PD-iMGL and human midbrain PD microglia. We conclude that LRRK2-G2019S iMGL serve as a model to study PD-related effects in human microglia.</p>}},
  author       = {{Ohtonen, Sohvi and Giudice, Luca and Jäntti, Henna and Fazaludeen, Mohammad Feroze and Shakirzyanova, Anastasia and Gómez-Budia, Mireia and Välimäki, Nelli Noora and Niskanen, Jonna and Korvenlaita, Nea and Fagerlund, Ilkka and Koistinaho, Jari and Amiry-Moghaddam, Mahmood and Savchenko, Ekaterina and Roybon, Laurent and Lehtonen, Šárka and Korhonen, Paula and Malm, Tarja}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-49294-9}},
  doi          = {{10.1038/s41598-023-49294-9}},
  volume       = {{13}},
  year         = {{2023}},
}