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

Sohvi Ohtonen; Luca Giudice; Henna Jäntti; Mohammad Feroze Fazaludeen; Anastasia Shakirzyanova; Mireia Gómez-Budia; Nelli Noora Välimäki; Jonna Niskanen; Nea Korvenlaita; Ilkka Fagerlund; Jari Koistinaho; Mahmood Amiry-Moghaddam; Ekaterina Savchenko; Laurent Roybon; Šárka Lehtonen; Paula Korhonen; Tarja Malm

doi:10.1038/s41598-023-49294-9

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

Sohvi Ohtonen, Luca Giudice, Henna Jäntti, Mohammad Feroze Fazaludeen, Anastasia Shakirzyanova, Mireia Gómez-Budia, Nelli Noora Välimäki, Jonna Niskanen, Nea Korvenlaita, Ilkka Fagerlund, Jari Koistinaho, Mahmood Amiry-Moghaddam, Ekaterina Savchenko, Laurent Roybon, Šárka Lehtonen, Paula Korhonen, Tarja Malm

Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift › Peer review

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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.

Originalspråk	engelska
Artikelnummer	22118
Tidskrift	Scientific Reports
Volym	13
Nummer	1
DOI	https://doi.org/10.1038/s41598-023-49294-9
Status	Published - 2023 dec.

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Ohtonen, S., Giudice, L., Jäntti, H., Fazaludeen, M. F., Shakirzyanova, A., Gómez-Budia, M., Välimäki, N. N., Niskanen, J., Korvenlaita, N., Fagerlund, I., Koistinaho, J., Amiry-Moghaddam, M., Savchenko, E., Roybon, L., Lehtonen, Š., Korhonen, P., & Malm, T. (2023). Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function. Scientific Reports, 13(1), Artikel 22118. https://doi.org/10.1038/s41598-023-49294-9

@article{0ba4fca431574733924b51347da2a664,

title = "Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson{\textquoteright}s disease related transcriptional profile and function",

abstract = "LRRK2-G2019S is one of the most common Parkinson{\textquoteright}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.",

author = "Sohvi Ohtonen and Luca Giudice and Henna J{\"a}ntti and Fazaludeen, {Mohammad Feroze} and Anastasia Shakirzyanova and Mireia G{\'o}mez-Budia and V{\"a}lim{\"a}ki, {Nelli Noora} and Jonna Niskanen and Nea Korvenlaita and Ilkka Fagerlund and Jari Koistinaho and Mahmood Amiry-Moghaddam and Ekaterina Savchenko and Laurent Roybon and {\v S}{\'a}rka Lehtonen and Paula Korhonen and Tarja Malm",

year = "2023",

month = dec,

doi = "10.1038/s41598-023-49294-9",

language = "English",

volume = "13",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Ohtonen, S, Giudice, L, Jäntti, H, Fazaludeen, MF, Shakirzyanova, A, Gómez-Budia, M, Välimäki, NN, Niskanen, J, Korvenlaita, N, Fagerlund, I, Koistinaho, J, Amiry-Moghaddam, M, Savchenko, E, Roybon, L, Lehtonen, Š, Korhonen, P & Malm, T 2023, 'Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function', Scientific Reports, vol. 13, nr. 1, 22118. https://doi.org/10.1038/s41598-023-49294-9

TY - JOUR

T1 - Human iPSC-derived microglia carrying the LRRK2-G2019S mutation show a Parkinson’s disease related transcriptional profile and function

AU - Ohtonen, Sohvi

AU - Giudice, Luca

AU - Jäntti, Henna

AU - Fazaludeen, Mohammad Feroze

AU - Shakirzyanova, Anastasia

AU - Gómez-Budia, Mireia

AU - Välimäki, Nelli Noora

AU - Niskanen, Jonna

AU - Korvenlaita, Nea

AU - Fagerlund, Ilkka

AU - Koistinaho, Jari

AU - Amiry-Moghaddam, Mahmood

AU - Savchenko, Ekaterina

AU - Roybon, Laurent

AU - Lehtonen, Šárka

AU - Korhonen, Paula

AU - Malm, Tarja

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-023-49294-9

DO - 10.1038/s41598-023-49294-9

M3 - Article

C2 - 38092815

AN - SCOPUS:85179714037

SN - 2045-2322

VL - 13

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 22118

ER -

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

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Ämnesklassifikation (UKÄ)

FN:s Globala mål

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