Zhang Hanrui, Reilly Muredach P
From the Division of Cardiology, Department of Medicine (H.Z., M.P.R.) and Irving Institute for Clinical and Translational Research (M.P.R.), Columbia University Medical Center, New York, NY.
Arterioscler Thromb Vasc Biol. 2017 Nov;37(11):2000-2006. doi: 10.1161/ATVBAHA.117.309195. Epub 2017 Oct 5.
Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases.
尽管人们高度认识到巨噬细胞在心血管代谢疾病中的关键作用，但由于缺乏用于细胞和基因研究的可靠且可扩展的模型，对人类巨噬细胞生物学的理解受到了阻碍。人诱导多能干细胞（iPSC）衍生的巨噬细胞（IPSDM）作为特定个体基因型细胞的无限来源，无疑将在推进我们对巨噬细胞在人类疾病中作用的理解方面发挥重要作用。在本综述中，我们总结了当前关于IPSDM在表型、功能和转录组水平上的分化和特征的文献。我们强调了在将iPSC分化为组织驻留巨噬细胞以及理解体外分化的IPSDM的个体发生方面所取得的进展，后者类似于原始造血而非成人确定性造血。我们回顾了IPSDM在孟德尔遗传疾病建模和宿主-病原体相互作用建模中的应用。最后，我们强调了在全基因组关联研究中使用IPSDM对冠状动脉疾病位点进行功能验证、功能基因组分析、药物测试以及心血管疾病细胞治疗等潜在研究领域。
