MicroRNAs (miRNAs) are small, ∼22 nucleotide, RNAs that have been shown to have a role in regulating gene expression during development in Caenorhabditis elegans and Drosophila. Although mammalian miRNAs have been identified, no function had been ascribed to them until this study, in Science, identified mouse miRNAs as regulators of haematopoiesis.

To investigate the importance of mammalian miRNAs in haematopoietic-cell development, Chen et al. cloned several miRNAs from mouse bone marrow, three of which — miR-181, miR-223 and miR-142 — showed preferential expression in haematopoietic tissue. Further analysis indicated that in the bone marrow, miR-181 was preferentially expressed by the B-lymphoid lineage compared with undifferentiated progenitor cells or other lineages. miR-142 was most highly expressed by B cells and myeloid cells, whereas miR-223 was preferentially expressed by myeloid lineage cells.

Can miRNAs regulate haematopoietic lineage commitment? Ectopic expression of miR-181 by undifferentiated progenitor cells from the bone marrow led to a selective increase in the number of B-lineage cells after in vitro culture, whereas miR-142 and miR-223 expression markedly enhanced the proportion of T-lineage cells. Further evidence of a role for miR-181 in B-lineage differentiation was provided by the observation that transfer of cells expressing miR-181 to lethally irradiated recipients led to a marked increase in the proportion of B-lineage cells in the peripheral blood and a concomitant decrease in the T-cell population, in particular among the CD8+ T-cell subset.

This study provides the first demonstration that miRNAs have a role in regulating development in mammals. Interestingly, although these miRNAs influenced the development of specific lymphoid populations, they did not completely block differentiation to other lineages, leading the authors to suggest that these individual miRNAs act as lineage modulators rather than as on/off switches.