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Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells.

Abstract：

: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.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Schmidt SI,Bogetofte H,Ritter L,Agergaard JB,Hammerich D,Kabiljagic AA,Wlodarczyk A,Lopez SG,Sørensen MD,Jørgensen ML,Okarmus J,Serrano AM,Kristensen BW,Freude K,Owens T,Meyer M

doi

10.1016/j.stemcr.2020.12.011

subject

Has Abstract

pub_date

2021-01-06 00:00:00

issn

2213-6711

pii

S2213-6711(20)30506-3

pub_type

杂志文章

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