A CRISPRi/a platform in human iPSC-derived microglia uncovers regulators of disease states

Microglia are emerging as key drivers of neurological diseases. However, we lack a systematic understanding of the underlying mechanisms. Here, we present a screening platform to systematically elucidate functional consequences of genetic perturbations in human induced pluripotent stem cell-derived microglia. We developed an efficient 8-day protocol for the generation of microglia-like cells based on the inducible expression of six transcription factors. We established inducible CRISPR interference and activation in this system and conducted three screens targeting the 'druggable genome'. These screens uncovered genes controlling microglia survival, activation and phagocytosis, including…

• NS
  National Science Foundation
• NI
  National Institutes of Health

  Awards: GM119139, F30 AG066418, MH115747, NS100717, ZO1 AG000534-02, U01 MH115747, DP2 GM119139, U54 NS100717, AG051390
• UO
  University of California, San Francisco
• NI
  National Institute on Aging

  Awards: F30 AG062043, F30 AG066418, R01 AG051390
• NI
  National Institute of Mental Health

  Award: U01 MH115747
• NI
  National Institute of General Medical Sciences

  Award: DP2 GM119139
• NI
  National Institute of Neurological Disorders and Stroke

  Award: U54 NS100717