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

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...

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Autores principales: Schmidt, Sissel Ida, Bogetofte, Helle, Ritter, Louise, Agergaard, Jette Bach, Hammerich, Ditte, Kabiljagic, Amina Arslanagic, Wlodarczyk, Agnieszka, Lopez, Silvia Garcia, Sørensen, Mia Dahl, Jørgensen, Mie Lærkegård, Okarmus, Justyna, Serrano, Alberto Martínez, Kristensen, Bjarne Winther, Freude, Kristine, Owens, Trevor, Meyer, Morten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878834/
https://www.ncbi.nlm.nih.gov/pubmed/33482100
http://dx.doi.org/10.1016/j.stemcr.2020.12.011
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author Schmidt, Sissel Ida
Bogetofte, Helle
Ritter, Louise
Agergaard, Jette Bach
Hammerich, Ditte
Kabiljagic, Amina Arslanagic
Wlodarczyk, Agnieszka
Lopez, Silvia Garcia
Sørensen, Mia Dahl
Jørgensen, Mie Lærkegård
Okarmus, Justyna
Serrano, Alberto Martínez
Kristensen, Bjarne Winther
Freude, Kristine
Owens, Trevor
Meyer, Morten
author_facet Schmidt, Sissel Ida
Bogetofte, Helle
Ritter, Louise
Agergaard, Jette Bach
Hammerich, Ditte
Kabiljagic, Amina Arslanagic
Wlodarczyk, Agnieszka
Lopez, Silvia Garcia
Sørensen, Mia Dahl
Jørgensen, Mie Lærkegård
Okarmus, Justyna
Serrano, Alberto Martínez
Kristensen, Bjarne Winther
Freude, Kristine
Owens, Trevor
Meyer, Morten
author_sort Schmidt, Sissel Ida
collection PubMed
description 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.
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spelling pubmed-78788342021-02-18 Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells Schmidt, Sissel Ida Bogetofte, Helle Ritter, Louise Agergaard, Jette Bach Hammerich, Ditte Kabiljagic, Amina Arslanagic Wlodarczyk, Agnieszka Lopez, Silvia Garcia Sørensen, Mia Dahl Jørgensen, Mie Lærkegård Okarmus, Justyna Serrano, Alberto Martínez Kristensen, Bjarne Winther Freude, Kristine Owens, Trevor Meyer, Morten Stem Cell Reports Article 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. Elsevier 2021-01-21 /pmc/articles/PMC7878834/ /pubmed/33482100 http://dx.doi.org/10.1016/j.stemcr.2020.12.011 Text en © 2020 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmidt, Sissel Ida
Bogetofte, Helle
Ritter, Louise
Agergaard, Jette Bach
Hammerich, Ditte
Kabiljagic, Amina Arslanagic
Wlodarczyk, Agnieszka
Lopez, Silvia Garcia
Sørensen, Mia Dahl
Jørgensen, Mie Lærkegård
Okarmus, Justyna
Serrano, Alberto Martínez
Kristensen, Bjarne Winther
Freude, Kristine
Owens, Trevor
Meyer, Morten
Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title_full Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title_fullStr Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title_full_unstemmed Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title_short Microglia-Secreted Factors Enhance Dopaminergic Differentiation of Tissue- and iPSC-Derived Human Neural Stem Cells
title_sort microglia-secreted factors enhance dopaminergic differentiation of tissue- and ipsc-derived human neural stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878834/
https://www.ncbi.nlm.nih.gov/pubmed/33482100
http://dx.doi.org/10.1016/j.stemcr.2020.12.011
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