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Ohtonen, Sohvi; Giudice, Luca; Jäntti, Henna; Fazaludeen, Mohammad Feroze; Shakirzyanova, Anastasia; Gómez-Budia, Mireia; Välimäki, Nelli-Noora; Niskanen, Jonna; Korvenlaita, Nea; Fagerlund, Ilkka; Koistinaho, Jari; Amiry-Moghaddam, Mahmood; Savchenko, Ekaterina; Roybon, Laurent; Lehtonen, Šárka; Korhonen, Paula; Malm, Tarja
Scientific reports, 12/2023, Letnik: 13, Številka: 1Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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