Published online before print December 8, 2006

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(Journal of Leukocyte Biology. 2007;81:711-719.)
© 2007 by Society for Leukocyte Biology

Quantitative expansion of ES cell-derived myeloid progenitors capable of differentiating into macrophages

Justin I. Odegaard^*, Divya Vats^*, Lina Zhang^*, Roberto Ricardo-Gonzalez^*, Kristi L. Smith^*, David B. Sykes^,, Mark P. Kamps and Ajay Chawla^*,1

^* Division of Endocrinology, Metabolism and Gerontology, Department of Medicine and Graduate Program in Immunology, Stanford University School of Medicine, Stanford, California, USA;
Department of Pathology and Molecular Pathology Graduate Program, University of California at San Diego, La Jolla, California, USA; and
Deparment of Medicine, Harvard Massachusetts General Hospital, Boston, Massachusetts, USA

¹ Correspondence: Division of Endocrinology, Metabolism and Gerontology, Department of Medicine and Graduate Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305-5103, USA. E-mail: achawla{at}stanford.edu

Macrophages participate in physiologic and pathologic processes through elaboration of distinct activation programs. Studies with macrophage cell systems have revealed much concerning the importance of this pleiotropic cell; however, these studies are inherently limited by three factors: heterogeneity of the target cell population, poor capacity to elaborate various activation programs, and lack of a genetically tractable model system for loss- and gain-of-function studies. Although definitive, hematopoietic lineages can be isolated from embryonic stem (ES) cells, these isolation procedures are inefficient and time-consuming and require elaborate cell-sorting protocols. We therefore examined whether myeloid precursors, capable of differentiating into macrophages, could be conditionally expanded in vitro. Here, we report methods for selective isolation and immortalization of ES cell-derived myeloid precursors by estrogen-regulated HoxA9 protein. Using this new macrophage differentiation system, an unlimited number of custom-designed macrophages with defined functional characteristics can be generated from any targeted ES cell. In combination with knockout or small interfering RNA knockdown technologies, this macrophage differentiation system provides a powerful tool for high throughput analysis of regulatory mechanisms controlling macrophage activation in health and disease.

Key Words: cell line • alternative activation • classical activation

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