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

doi:10.1016/j.stemcr.2021.03.010

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 journal › Article › peer-review

39 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 language	English
Pages (from-to)	1363-1380
Number of pages	18
Journal	Stem Cell Reports
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2021.03.010
State	Published - 11 May 2021

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.stemcr.2021.03.010

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title = "Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors",

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.",

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author = "Chen, {Shih Wei} and Hung, {Yu Sheng} and Fuh, {Jong Ling} and Chen, {Nien Jung} and Chu, {Yeh Shiu} and Chen, {Shu Cian} and Fann, {Ming Ji} and Wong, {Yu Hui}",

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year = "2021",

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doi = "10.1016/j.stemcr.2021.03.010",

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T1 - Efficient conversion of human induced pluripotent stem cells into microglia by defined transcription factors

AU - Chen, Shih Wei

AU - Hung, Yu Sheng

AU - Fuh, Jong Ling

AU - Chen, Nien Jung

AU - Chu, Yeh Shiu

AU - Chen, Shu Cian

AU - Fann, Ming Ji

AU - Wong, Yu Hui

PY - 2021/5/11

Y1 - 2021/5/11

N2 - 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.

AB - 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.

KW - CEBPA

KW - induced microglia

KW - induced pluripotent stem cells

KW - reprogramming

KW - SPI1/PU.1

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DO - 10.1016/j.stemcr.2021.03.010

M3 - Article

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SN - 2213-6711

VL - 16

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EP - 1380

JO - Stem Cell Reports

JF - Stem Cell Reports

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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