Direct induction of ramified microglia-like cells from human monocytes: dynamic microglial dysfunction in Nasu-Hakola disease.
Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders.
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Masahiro
M
Ohgidani
1] Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University [2] Innovation Center for Medical Redox Navigation, Kyushu University.
Takahiro A
TA
Kato
Innovation Center for Medical Redox Navigation, Kyushu University.
Daiki
D
Setoyama
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Noriaki
N
Sagata
1] Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University [2] Department of Psychiatry, Osaka University Graduate School of Medicine.
Ryota
R
Hashimoto
Department of Psychiatry, Asakayama General Hospital.
Kazue
K
Shigenobu
Department of Psychiatry, Osaka University Graduate School of Medicine.
Tetsuhiko
T
Yoshida
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Kohei
K
Hayakawa
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Norihiro
N
Shimokawa
Innovation Center for Medical Redox Navigation, Kyushu University.
Daisuke
D
Miura
Innovation Center for Medical Redox Navigation, Kyushu University.
Hideo
H
Utsumi
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University.
Shigenobu
S
Kanba
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D008060:Lipodystrophy / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010009:Osteochondrodysplasias / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D013344:Subacute Sclerosing Panencephalitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D018836:Inflammation Mediators; D008565:Membrane Proteins; C110546:TYROBP protein, human