Specialized tissue microenvironments direct and maintain the development of hematopoietic stem cells, but the cellular and molecular interactions of this process are still being determined. In Cell, Calderon and Boehm use a modular approach to delineate the rules of hematopoiesis. Through reconstitution of the thymic epithelium of nude mice that lack hematopoietic function with various combinations of chemokines (CCL25 and CXCL12), the cytokine SCF and the Notch ligand DLL4, the thymic epithelium is made functional to support different progenitor populations. For example, CXCL12, DLL4 and SCF together support T cell progenitors, whereas CCL25, CXCL12 and SCF are biased toward B cells. In total, the authors generate 15 different combinations of factors, each with its own functionality. This study identifies the surprisingly minimalist rules that can govern hematopoiesis.

Cell 149, 159–172 (2012)