Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors

Shih Wei Chen, Yu Sheng Hung, Jong Ling Fuh, Nien Jung Chen, Yeh Shiu Chu, Shu Cian Chen, Ming Ji Fann, Yu Hui Wong*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Microglia, the immune cells of the central nervous system, play critical roles in brain physiology and pathology. We report a novel approach that produces, within 10 days, the differentiation of human induced pluripotent stem cells (hiPSCs) into microglia (iMG) by forced expression of both SPI1 and CEBPA. High-level expression of the main microglial markers and the purity of the iMG cells were confirmed by RT-qPCR, immunostaining, and flow cytometry analyses. Whole-transcriptome analysis demonstrated that these iMGs resemble human fetal/adult microglia but not human monocytes. Moreover, these iMGs exhibited appropriate physiological functions, including various inflammatory responses, ADP/ATP-evoked migration, and phagocytic ability. When co-cultured with hiPSC-derived neurons, the iMGs respond and migrate toward injured neurons. This study has established a protocol for the rapid conversion of hiPSCs into functional iMGs, which should facilitate functional studies of human microglia using different disease models and also help with drug discovery.

Original languageEnglish
Pages (from-to)1363-1380
Number of pages18
JournalStem Cell Reports
Volume16
Issue number5
DOIs
StatePublished - 11 May 2021

Keywords

  • CEBPA
  • induced microglia
  • induced pluripotent stem cells
  • reprogramming
  • SPI1/PU.1

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