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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; Fagerlund, Ilkka; Koistinaho, Jari; Amiry-Moghaddam, Mahmood; Savchenko, Ekaterina; Roybon, Laurent; Lehtonen, Sárka; Korhonen, Paula; Malm, Tarja.
Afiliação
  • Ohtonen S; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland. sohvi.ohtonen@uef.fi.
  • Giudice L; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Jäntti H; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Fazaludeen MF; F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
  • Shakirzyanova A; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Gómez-Budia M; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Välimäki NN; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Niskanen J; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Korvenlaita N; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Fagerlund I; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Koistinaho J; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Amiry-Moghaddam M; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Savchenko E; A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Roybon L; Neuroscience Center, University of Helsinki, Helsinki, Finland.
  • Lehtonen S; Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  • Korhonen P; Stem Cell Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Lund University, Lund, Sweden.
  • Malm T; Stem Cell Laboratory for CNS Disease Modeling, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Sci Rep ; 13(1): 22118, 2023 12 13.
Article em En | MEDLINE | ID: mdl-38092815
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 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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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença de Parkinson / Células-Tronco Pluripotentes Induzidas Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article