HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print December 8, 2006

This Article Full Text (Reprint (PDF)) All Versions of this Article: jlb.0906590v1 81/3/711    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Odegaard, J. I. Articles by Chawla, A. Search for Related Content PubMed PubMed Citation Articles by Odegaard, J. I. Articles by Chawla, A.

© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906590

Received for publication September 28, 2006.
Revised November 9, 2006.
Accepted for publication November 14, 2006.

Article

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 ^*@

*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

^@ To whom correspondence should be addressed. E-mail: achawla{at}stanford.edu.

	Abstract

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: activation