Modeling Normal and Disordered Human Hematopoiesis

Abstract

Similarities between the organization of the blood-forming system in humans and mice, and the ease of genetically manipulating and assessing primitive mouse hematopoietic cells, has made this species a model of choice. However, important differences exist in the role of specific gene products in regulating analogous steps in the generation of particular blood cell types in humans and mice, as well as in the perturbations that the same mutations elicit in hematopoietic cells from the two species. At the same time, the methods to generate and propagate normal and genetically altered human hematopoietic cells are increasingly permissive, and progress towards humanized mice is advancing rapidly. We review the incomplete fidelity of the mouse system in modeling human hematopoiesis, and highlight advances that portend a shift towards studies focused directly on human cells.