Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function
(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.
(Less)
- author
- organization
- publishing date
- 2023-12
- 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
- 2024-06-28 14:31:39
@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}}, }