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*

*此作品的通信作者

研究成果: Article同行評審

34 引文 斯高帕斯(Scopus)

摘要

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.

原文English
頁(從 - 到)1363-1380
頁數18
期刊Stem Cell Reports
16
發行號5
DOIs
出版狀態Published - 11 5月 2021

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