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

2021; Elsevier BV; Volume: 16; Issue: 5 Linguagem: Inglês

10.1016/j.stemcr.2021.03.010

2213-6711

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

Immune cells in cancer

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.