Stem-cell-derived human microglia transplanted in mouse brain to study human disease

Nat Neurosci. 2019 Dec;22(12):2111-2116. doi: 10.1038/s41593-019-0525-x. Epub 2019 Oct 28.

Abstract

Although genetics highlights the role of microglia in Alzheimer's disease, one-third of putative Alzheimer's disease risk genes lack adequate mouse orthologs. Here we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human-specific Alzheimer's disease risk genes. Oligomeric amyloid-β induces a divergent response in human versus mouse microglia. This model can be used to study the role of microglia in neurological diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Cell Differentiation
  • Embryonic Stem Cells / cytology*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / drug effects
  • Microglia / metabolism*
  • Microglia / transplantation*
  • Transcriptome*

Substances

  • Amyloid beta-Peptides