Doulatov, S. et al. Cell Stem Cell 13, 459–470 (2013).

Human pluripotent stem cells (hPSCs) can be differentiated along the blood lineage, but long-term repopulation of hematopoietic stem cells with multilineage differentiation potential remains elusive. Doulatov et al. describe a promising strategy to achieve this goal. Starting with hPSC-derived hematopoietic progenitors, they screened a set of known transcriptional regulators and identified three—HOXA9, ERG and RORA—that promoted self-renewal and increased the differentiation potential of the cells in vitro. Two additional factors, SOX4 and MYB, yielded hPSC-derived cells with short-term engraftment potential and with myeloid and erythroid lineage potential in vivo. Further factors may in the future reconstitute more complete blood stem cell function in hPSC-derived cells, enabling a broadened scope for their application in disease modeling and drug screening.