TY - JOUR
T1 - Emerging Developments in Human Induced Pluripotent Stem Cell-Derived Microglia
T2 - Implications for Modelling Psychiatric Disorders With a Neurodevelopmental Origin
AU - Hanger, Bjørn
AU - Couch, Amalie
AU - Rajendran, Lawrence
AU - Srivastava, Deepak P
AU - Vernon, Anthony C
N1 - Copyright © 2020 Hanger, Couch, Rajendran, Srivastava and Vernon.
PY - 2020/8/23
Y1 - 2020/8/23
N2 - Microglia, the resident tissue macrophages of the brain, are increasingly implicated in the pathophysiology of psychiatric disorders with a neurodevelopmental origin, including schizophrenia. To date, however, our understanding of the potential role for these cells in schizophrenia has been informed by studies of aged post-mortem samples, low resolution in vivo neuroimaging and rodent models. Whilst these have provided important insights, including signs of the heterogeneous nature of microglia, we currently lack a validated human in vitro system to characterize microglia in the context of brain health and disease during neurodevelopment. Primarily, this reflects a lack of access to human primary tissue during developmental stages. In this review, we first describe microglia, including their ontogeny and heterogeneity and consider their role in brain development. We then provide an evaluation of the potential for differentiating microglia from human induced pluripotent stem cells (hiPSCs) as a robust in vitro human model system to study these cells. We find the majority of protocols for hiPSC-derived microglia generate cells characteristically similar to foetal stage microglia when exposed to neuronal environment-like cues. This may represent a robust and relevant model for the study of cellular and molecular mechanisms in schizophrenia. Each protocol however, provides unique benefits as well as shortcomings, highlighting the need for context-dependent protocol choice and cross-lab collaboration and communication to identify the most robust and translatable microglia model.
AB - Microglia, the resident tissue macrophages of the brain, are increasingly implicated in the pathophysiology of psychiatric disorders with a neurodevelopmental origin, including schizophrenia. To date, however, our understanding of the potential role for these cells in schizophrenia has been informed by studies of aged post-mortem samples, low resolution in vivo neuroimaging and rodent models. Whilst these have provided important insights, including signs of the heterogeneous nature of microglia, we currently lack a validated human in vitro system to characterize microglia in the context of brain health and disease during neurodevelopment. Primarily, this reflects a lack of access to human primary tissue during developmental stages. In this review, we first describe microglia, including their ontogeny and heterogeneity and consider their role in brain development. We then provide an evaluation of the potential for differentiating microglia from human induced pluripotent stem cells (hiPSCs) as a robust in vitro human model system to study these cells. We find the majority of protocols for hiPSC-derived microglia generate cells characteristically similar to foetal stage microglia when exposed to neuronal environment-like cues. This may represent a robust and relevant model for the study of cellular and molecular mechanisms in schizophrenia. Each protocol however, provides unique benefits as well as shortcomings, highlighting the need for context-dependent protocol choice and cross-lab collaboration and communication to identify the most robust and translatable microglia model.
KW - autism
KW - human induced pluripotent stem cells
KW - microglia
KW - neurodevelopmental disorders
KW - neuroinflammation
KW - schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85090111258&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2020.00789
DO - 10.3389/fpsyt.2020.00789
M3 - Review article
C2 - 32848951
SN - 1664-0640
VL - 11
SP - 789
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 789
ER -