Early hematopoiesis occurs in the fetal liver but transitions to the bone marrow at later stages of development. Distinct innate-like lymphocytes arise from the fetal liver progenitors, but what distinguishes fetal cells from adult cells has remained unknown. In Science, Muljo and colleagues show that differences in the expression of Lin28 microRNA regulate fetal hematopoiesis in both mice and humans. Lin28 suppresses the Let-7 family of microRNA, present in abundance in adult hematopoietic progenitor cells. Ectopic expression of Lin28 transforms adult bone-marrow-cell potential to that arising from fetal liver–derived progenitors. These include more production of innate-like B-1a cells and marginal-zone B cells, certain γδ T cells and PLZF+ invariant natural killer cells. These findings provide a mechanistic basis for the distinct waves of lymphocyte development that occur during ontogeny.

Science (16 February 2012) 10.1126/science.1216557