TY - JOUR
T1 - Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
AU - Schmidt, Sissel Ida
AU - Bogetofte, Helle
AU - Ritter, Louise
AU - Agergaard, Jette Bach
AU - Hammerich, Ditte
AU - Kabiljagic, Amina Arslanagic
AU - Wlodarczyk, Agnieszka
AU - Lopez, Silvia Garcia
AU - Sørensen, Mia Dahl
AU - Jørgensen, Mie Lærkegård
AU - Okarmus, Justyna
AU - Serrano, Alberto Martínez
AU - Kristensen, Bjarne Winther
AU - Freude, Kristine
AU - Owens, Trevor
AU - Meyer, Morten
PY - 2021
Y1 - 2021
N2 - Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem cell-derived human neural stem cells (NSCs). The effect was consistent across different NSC and microglial cell lines and was independent of prior microglial activation, although restricted to microglia of embryonic origin. We provide evidence that the effect is mediated through reduced cell proliferation and decreased apoptosis and necrosis orchestrated in a sequential manner during the differentiation process. tumor necrosis factor alpha, interleukin-1β, and insulinlike growth factor 1 are identified as key mediators of the effect and shown to directly increase dopaminergic differentiation of human NSCs. These findings demonstrate a positive effect of microglia on dopaminergic neurogenesis and may provide new insights into inductive and protective factors that can stimulate in vitro derivation of dopaminergic neurons.
AB - Microglia have recently been established as key regulators of brain development. However, their role in neuronal subtype specification remains largely unknown. Using three different co-culture setups, we show that microglia-secreted factors enhance dopaminergic differentiation of somatic and induced pluripotent stem cell-derived human neural stem cells (NSCs). The effect was consistent across different NSC and microglial cell lines and was independent of prior microglial activation, although restricted to microglia of embryonic origin. We provide evidence that the effect is mediated through reduced cell proliferation and decreased apoptosis and necrosis orchestrated in a sequential manner during the differentiation process. tumor necrosis factor alpha, interleukin-1β, and insulinlike growth factor 1 are identified as key mediators of the effect and shown to directly increase dopaminergic differentiation of human NSCs. These findings demonstrate a positive effect of microglia on dopaminergic neurogenesis and may provide new insights into inductive and protective factors that can stimulate in vitro derivation of dopaminergic neurons.
U2 - 10.1016/j.stemcr.2020.12.011
DO - 10.1016/j.stemcr.2020.12.011
M3 - Journal article
C2 - 33482100
VL - 16
SP - 1
EP - 14
JO - Stem Cell Reports
JF - Stem Cell Reports
SN - 2213-6711
ER -