Microglia have emerged in recent years as primary modulators of both development and pathogenesis of the nervous system, urgently requiring study. However, unlike bone marrow and monocyte-derived macrophages, primary human microglia remain poorly characterized as they differ greatly from mature mouse microglia, are not easily accessible and current methods employed for isolation likely alter their defining characteristics6. In vitro approaches to model and study CNS disorders using human iPS and ES derived cultures are currently lacking this important component. Robust protocols have been developed to induce human ES or iPS cells to differentiate into the different neuroectodermal cell types of the CNS including neurons, astrocytes and oligodendrocytes 7,8. Protocols recapitulating classical hematopoiesis, followed by expansion of monocytes have shown that myeloid cells can be generated from mouse and human ES cells 9. However, generation of microglia-like cells matching the recently identified signatures of acutely isolated microglia 10,11, and following their non-monocytic yolk sac ontogeny 4, has not been reported from pluripotent human cells.
