Emergence of muscle and neural hematopoiesis in humans

During human development, hematopoiesis is thought to be compartmentalized to the fetal circulation, liver, and bone marrow. Here, we show that combinations of cytokines together with bone morphogenetic protein-4 and erythropoietin could induce multiple blood lineages from human skeletal muscle or neural tissue. Under defined serum-free conditions, the growth factors requirements, proliferation, and differentiation capacity of muscle and neural hematopoiesis were distinct to that derived from committed hematopoietic sites and were uniquely restricted to CD45(-)CD34(-) cells expressing the prominin AC133. Our study defines epigenetic factors required for the emergence of hematopoiesis from unexpected tissue origins and illustrates that embyronically specified microenvironments do not limit cell fate in humans.