Premium
Quantitative expansion of ES cell‐derived myeloid progenitors capable of differentiating into macrophages
Author(s) -
Odegaard Justin I.,
Vats Divya,
Zhang Lina,
RicardoGonzalez Roberto,
Smith Kristi L.,
Sykes David B.,
Kamps Mark P.,
Chawla Ajay
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0906590
Subject(s) - biology , microbiology and biotechnology , myeloid , progenitor cell , myeloid cells , immunology , stem cell
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.