A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-culture-Specific Expression Profile and Inflammatory Response

Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons. Co-cultures retain neuronal maturity and functionality for many weeks.…

• W
  Wellcome

  Awards: WTISSF121302, 090532/Z/09/Z
• WT
  Wellcome Trust

  Award: WTISSF121302
• EF
  European Federation of Pharmaceutical Industries and Associations
• AR
  Alzheimer's Research Trust
• NI
  National Institute for Health and Care Research
• RS
  Royal Society
• PU
  Parkinson's UK

  Awards: 2581970, SC037554
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

  Award: 148607
• AR
  Alzheimer’s Research UK
• IM
  Innovative Medicines Initiative

  Award: 115439
• SF
  Seventh Framework Programme

  Award: 115439
• MR
  Medical Research Council

  Awards: MR/L023784/2, MR/N013255/1, MC_PC_16034, G0900747 91070, MR/M024962/1, MR/N013255/1, MC_PC_16034, MC_EX_MR/N50192X/1, MC_EX_MR/N50192X/1, MR/L023784/1
• OM
  Oxford Martin School, University of Oxford

  Award: LC0910-004
• SF
  Seventh Framework Programme

  Award: FP7/2007e2013