Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson's disease related transcriptional profile and function.
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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. |
Year of Publication | 2023
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Journal | Scientific reports
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Volume | 13
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Issue | 1
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Pages | 22118
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Date Published | 12/2023
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ISSN | 2045-2322
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DOI | 10.1038/s41598-023-49294-9
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PubMed ID | 38092815
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