Directed Differentiation of Human Pluripotent Stem Cells to Microglia

被引：242

作者：

Douvaras, Panagiotis ^{[1
]}

Sun, Bruce ^{[1
]}

Wang, Minghui ^{[2
]}

Kruglikov, Ilya ^{[1
]}

Lallos, Gregory ^{[1
]}

Zimmer, Matthew ^{[1
]}

Terrenoire, Cecile ^{[1
]}

Zhang, Bin ^{[2
]}

Gandy, Sam ^{[3
]}

Schadt, Eric ^{[2
]}

Freytes, Donald O. ^{[4
,5
]}

Noggle, Scott ^{[1
]}

Fossati, Valentina ^{[1
]}

机构：

[1] New York Stem Cell Fdn Res Inst, New York, NY 10019 USA

[2] Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA

[3] Icahn Sch Med Mt Sinai, Alzheimers Dis Res Ctr, Dept Psychiat, Dept Neurol, New York, NY 10029 USA

[4] North Carolina State Univ, Joint Dept Biomed Engn, Raleigh, NC 27695 USA

[5] Univ North Carolina Chapel Hill, Raleigh, NC 27695 USA

来源：

STEM CELL REPORTS | 2017年 / 8卷 / 06期

关键词：

BRAIN-INJURY; IN-VIVO; CNS; HEMATOPOIESIS; EXPRESSION; REVEALS; DISEASE; MOUSE; MYB;

D O I：

10.1016/j.stemcr.2017.04.023

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs). Further differentiation of the progenitors resulted in ramified microglia with highly motile processes, expressing typical microglial markers. Analyses of gene expression and cytokine release showed close similarities between iPSC-derived (iPSC-MG) and human primary microglia as well as clear distinctions from macrophages. iPSC-MG were able to phagocytose and responded to ADP by producing intracellular Ca2+ transients, whereas macrophages lacked such response. The differentiation protocol was highly reproducible across several pluripotent stem cell lines.

引用

页码：1516 / 1524

页数：9

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